Note: Descriptions are shown in the official language in which they were submitted.
VGiJG 1 1 / V,-V 1 VrL/1
L f' t/ 1 V'+G l
CA 02403563 2002-09-19
Novel a-Sulfin- and a-Sulfonamino Acid Amides
The present invention relates to novel a-sulftn- and a-sulfonamino acid amides
of formula t
below. (t relates to the preparation of those substances and to agrochemical
compositions
comprising at least one of those compounds as active ingredient. The invention
relates also
to the preparation of the said compositions and to the use of the compounds or
of the
compositions in controlling or preventing the infestation of plants by
phytopathogenic
microorganisms, especially fungi.
The invention relates to a-sulfin- and a-sulfonamino acid amides of the
general formula 1
R2 O R4 Rg
_~I1_)~ ~ R8
Ri S H H ~ ~~ O R,o Ct)
O Ra Rs R.r Re 3
including the optical isomers thereof and mixtures of such isomers,
wherein
"Y'.~,~tro~k or
n is a number zero or one;
R, is C,-C,2alkyl, C,-C,aatkyl substituted with C,-C,alkoxy, C,-C4alkytthio,
C,-Csalkytsulfonyl,
C3-Cecycloalkyl, cyano, C,-Cgalkoxycarbonyl, C3-Csalkenytoxycarbonyt or
C3-Csalkynytoxycarbonyl; C3-Cecycloalkyl; CZ-C,Zalkenyi; C~-C,Zalkynyl; C,-
C,2halogenalkyl; . . _
or a group NR"R,2 wherein R" and R,2 are each independently of the other~C~-
Csalkyl, or
together are tetra- or penta-methytene;
R2 and R3 are each independently hydrogen; C,-CBalkyl; C,-Ceatkyl substituted
with hydroxy,
mercapto, C~-C4alkoxy or C,-C4atkyithio; C3-Cealkenyt; C3-Cealkynyl; C3-
Cecycloalkyl;
C3-Cecycloalkyl-C,-C4alkyl; or the two groups R2 and R3 together with the
carbon atom to
which they are bonded form a three- to eight-membered hydrocarbon ring;
R4 , Rs , Rg and R~ are each independently hydrogen or C,-C4alkyl; . .
R8 is hydrogen or an organic radical;
R9 is an organic radical;
AMENDED SHEET
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-2
R,s R,3 R,s R,s R,3 R,s
R,o is either hydrogen , -~ - R,S , -C-l=~R,S , -C-R~8 , -C--~-R~8
R,a R,a R,~ R,a R,a R,s
R,s R,s
or - ~ -~Z-R,8 , wherein
R,a R,s
R,3, R,a, R,s, R" and R,s are each independently hydrogen or C,-Caalkyl,
R,5 is Ca-C,2alkyl; C,-C,2halogenalkyl; C3-Cecycloalkyl; optionally
substituted aryl or
optionally substituted heteroaryl,
R,e is optionally substituted aryl or optionally substituted heteroaryl; and
Z is oxygen, sulfur -CR2oR2,- or -NR22-, wherein R2o, R2, and Rz2
independently of each
other are hydrogen or C,-Caalkyl;
provided that when Ra is hydrogen, Rs is not C,-Cs-alkoxy, C3-Csalkenyloxy or
C3-Cs-alkynyloxy in position 3 of the phenyl ring carrying these radicals.
In the above definition aryl includes aromatic hydrocarbon rings like phenyl,
naphthyl,
anthracenyl, phenanthrenyl, with phenyl being preferred.
Heteroaryl stands for aromatic ring systems comprising mono-, bi- or tricyclic
systems
wherein at least one oxygen, nitrogen or sulfur atom is present as a ring
member. Examples
are furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl,
oxazolyl, isoxazolyl,
oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl,
pyrimidinyl, pyrazinyl,
triazinyl, tetrazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl,
indazolyl,
benzotriazolyl, benzothiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,
phthalazinyl, quin-
oxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl.
The above aryl and heteroaryl groups may carry one or more identical or
different
substituents. Normally not more than three substituents are present at the
same time.
Examples of substituents of aryl or heteroaryl groups are: alkyl, alkenyl,
alkynyl, cycloalkyl,
cycloalkyl-alkyl, phenyl and phenyl-alkyl, it being possible in turn for all
of the preceding
groups to carry one or more identical or different halogen atoms; alkoxy;
alkenyloxy;
alkynyloxy; alkoxyalkyl; halogenalkoxy, alkylthio; halogenalkylthio;
alkylsulfonyl; formyl;
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-3
alkanoyl; hydroxy; halogen; cyano; nitro; amino; alkylamino; dialkylamino;
carboxy;
alkoxycarbonyl; alkenyloxycarbonyl; alkynyloxycarbonyl.
In the above definitions "halogen" or the prefix "halo" includes fluorine,
chlorine, bromine
and iodine.
The alkyl, alkenyl and alkynyl radicals may be straight-chain or branched.
This applies also
to the alkyl, alkenyl or alkynyl parts of other alkyl-, alkenyl- or alkynyl-
containing groups.
The organic radical in R$ and R9 indicates that practically every substituent
used in the art of
organic chemistry may be placed in the indicated position at the phenylene
bridge member.
Preferred are however the more frequently used radicals like C,-Cealkyl, C2-
CSalkenyl,
C2-Cealkynyl, C3-Cecycloalkyl, C3-CBCycloalkyl-C,-C4alkyl, C,-Cealkylthio, C,-
Cealkylsulfonyl,
C,-Caalkoxy, C3-Csalkenyloxy, C3-Csalkynyloxy, C3-Cecycloalkoxy, C,-CBalkoxy-
C,-C4alkyl,
C,-Cealkoxycarbonyl, C3-Cealkenyloxycarbonyl, C3-Cealkynyloxycarbonyl, C,-
CBalkanoyl,
C,-Cedialkylamino, C,-Cealkylamino wherein in each of the above radicals the
alkyl, alkenyl,
alkynyl or cycloalkyl groups may be partially or fully halogenated; carboxy,
formyl, halogen,
nitro, cyano, hydroxy or amino.
Depending upon the number of carbon atoms mentioned, alkyl on its own or as
part of
another substituent is to be understood as being, for example, methyl, ethyl,
propyl, butyl,
pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl and the isomers
thereof, for
example isopropyl, isobutyl, tert-butyl or sec-butyl, isopentyl or tert-
pentyl.
Cycloalkyl is, depending upon the number of carbon atoms mentioned,
cyclopropyl, cyclo-
butyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.
Depending upon the number of carbon atoms mentioned, alkenyl as a group or as
a struc-
tural element of other groups is to be understood as being, for example,
ethenyl, allyl,
1-propenyl, buten-2-yl, buten-3-yl, penten-1-yl, penten-3-yl, hexen-1-yl, 4-
methyl-3-pentenyl
or 4-methyl-3-hexenyl.
Alkynyl as a group or as a structural element of other groups is, for example,
ethynyl,
propyn-1-yl, propyn-2-yl, butyn-1-yl, butyn-2-yl, 1-methyl-2-butynyl, hexyn-1-
yl, 1-ethyl-2-
butynyl or octyn-1-yl.
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-4
A halogenalkyl group may contain one or more (identical or different) halogen
atoms, and
for example may stand for CHC12, CH2F, CC13, CH2C1, CHF2, CF3, CH2CH2Br,
C2C15, CH2Br,
CHCIBr, CF3CH2, etc..
Where R2 and R3 together with the carbon atom to which they are attached form
a
hydrocarbon ring the ring corresponds to cyclopropane, cyclobutane,
cyclopentane,
cyclohexane, cycloheptane or cyclooctane
The presence of at least one asymmetric carbon atom and/or at least one
asymmetric
oxidized sulfur atom in the compounds of formula I means that the compounds
may occur in
optically isomeric forms. As a result of the presence of a possible aliphatic
C=C double
bond, geometric isomerism may also occur. Formula I is intended to include all
those
possible isomeric forms and mixtures thereof.
Preferred subgroups of compounds of formula I are those wherein
n is one; or
R, is C,-C,2alkyl, C,-C,2alkyl substituted with C,-C4alkoxy, C,-C4alkylthio,
or
C,-C4alkylsulfonyl; C3-Cecycloalkyl; C2-C,2alkenyl; Cz-C,2alkynyl; C,-
C,2halogenalkyl; or a
group NR"R,2 wherein R" and R,2 are each independently of the other hydrogen
or
C,-Csalkyl, or together are tetra- or penta-methylene; or
R, is C,-C,2alkyl, C2-C,2alkenyl; C,-C,2halogenalkyl; or a group NR"R,2
wherein R"
and R,2 are each independently of the other hydrogen or C,-Csalkyl; or
R, is C,-C4alkyl, C2-C4alkenyl; C,-C4halogenalkyl; or C,-C2dialkylamino; or
R, is C,-C4alkyl, vinyl; C,-C4halogenalkyl; or dimethylamino; or
R2 is hydrogen and R3 is C,-CBalkyl, C,-Cealkyl optionally substituted by
hydroxy,
C,-C4alkoxy, mercapto or C,-C4alkylthio; C3-Caalkenyl; C3-C$alkynyl; C3-
CBcycloalkyl or
C3-Cecycloalkyl-C,-C4alkyl; or
R2 is hydrogen and R3 is C,-C4alkyl; C3-C4alkenyl or cyclopropyl; or
R2 is hydrogen and R3 is C3-C4alkyl; allyl or cyclopropyl; or
R2 is hydrogen and R3 is isopropyl; or
R4 is hydrogen, methyl or ethyl; or
R4 is hydrogen or methyl; or
R4 is hydrogen; or
R5, R6 and R, are each independently hydrogen or methyl; or
RS , R6 and R, are each hydrogen; or
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-5
R8 is hydrogen, C,-Ca-alkyl, C2-CBalkenyl, C2-Cealkynyl, C3-Cecycloalkyl,
C3-Cecycloalkyl-C,-C4alkyl, C,-CBalkylthio, C,-Cealkylsulfonyl, C,-CBalkoxy,
C3-CBalkenyloxy,
C3-Cealkynyloxy, C3-CBcycloalkoxy, C,-Cealkoxy-C,-C4alkyl, C,-
Cealkoxycarbonyl,
C3-Cealkenyloxycarbonyl, C3-Cealkynyloxycarbonyl, C,-Cealkanoyl, C,-
Cedialkylamino,
C,-Cgalkylamino wherein in each of the above radicals the alkyl, alkenyl,
alkynyl or
cycloalkyl groups may be partially or fully halogenated; carboxy, formyl,
halogen, nitro,
cyano, hydroxy or amino; or
Rg is hydrogen, C,-CBalkyl, C,-CBhalogenalkyl, C2-Cealkenyl, C2-Cealkynyl,
C,-CBalkylthio, C,-CBhalogenalkylthio, C,-Cealkoxy, C,-Cehalogenalkoxy, C,-
Cealk-
oxy-C,-C4alkyl, C,-Cealkoxycarbonyl, C,-Cealkanoyl, formyl, halogen, nitro,
cyano or
hydroxy; or
R$ is hydrogen, C,-C4alkyl, C,-C4halogenalkyl, C,-C4alkoxy, C,-
C4alkoxycarbonyl,
C,-C4alkanoyl, formyl, halogen, cyano or hydroxy; or
Re is hydrogen, C,-C4alkyl, halogen or cyano; or
R9 is C,-Cealkyl, C2-Cealkenyl, C2-Cealkynyl, C3-Cecycloalkyl, C3-Cecyclo-
alkyl-C,-C4alkyl, C,-Cealkylthio, C,-CBalkylsulfonyl, C,-Cealkoxy, C3-
CBalkenyloxy,
C3-Cealkynyloxy, C3-CBCycloalkoxy, C,-CBalkoxy-C,-C4alkyl, C,-
CBalkoxycarbonyl,
C3-CBalkenyloxycarbonyl, C3-Caalkynyloxycarbonyl, C,-CBalkanoyl, C,-
CBdialkylamino,
C,-Cealkylamino wherein in each of the above radicals the alkyl, alkenyl,
alkynyl or
cycloalkyl groups may be partially or fully halogenated; carboxy, formyl,
halogen, nitro,
cyano, hydroxy or amino, provided that when R8 is hydrogen, R9 is not C,-
Csalkoxy, C3-Csal-
kenyloxy or C3-Csalkynyloxy in position 3 of the phenyl ring carrying these
radicals ; or
R9 is C,-C4alkyl, C,-C4halogenalkyl, C,-C4alkoxy, C,-C4alkoxycarbonyl, C,-
C4alkanoyl,
formyl, halogen, cyano or hydroxy, provided that when Re is hydrogen, R9 is
not C,-Csalkoxy
in position 3 of the phenyl ring carrying these radicals; or
R9 is C,-C4alkyl, halogen or cyano; or
R,3, R,4, R,6, R" and R,9 are each independently hydrogen or methyl; or
R,3, R,4, R,6, R" and R,9 are each hydrogen; or
R,5 is C4-C,2alkyl; C,-C,2halogenalkyl; C3-Cecycloalkyl; optionally
substituted aryl or
optionally substituted heteroaryl consisting of one or two condensed five or
six membered
rings with 1 to 4 identical or different heteroatoms selected from oxygen,
nitrogen or sulfur;
or
R,5 is C4-C,2alkyl; C,-C,2halogenalkyl; C3-Cacycloalkyl; phenyl, naphthyl,
furyl, thienyl,
pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, thiazolyl,
pyridyl, pyridazinyl,
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-6
pyrimidinyl, pyrazinyl, triazinyl, indolyl, benzothiophenyl, benzofuranyl,
benzimidazolyl,
benzthiazolyl, benzoxazolyl or quinolyl with each of the aromatic ring being
optionally
substituted by 1 to 3 substituents selected from the group consisting of C,-
CBalkyl,
C2-Cealkenyl, C2-CBalkynyl, C3-CBcycloalkyl, C3-CBcycloalkyl-C,-C4alkyl,
phenyl,
phenyl-C,-C4alkyl wherein the hydrogens of all these substituents may be
optionally
substituted by one or more identical or different halogen atoms; C,-C-alkoxy,
C3-Cealken-
yloxy, C3-CBalkynyloxy, C,-Cealkoxy-C,-C4alkyl, C,-CBhalogenalkoxy, C,-
Cealkylthio,
C,-CBhalogenalkylthio, C,-Cealkylsulfonyl, formyl, C2-C8-alkanoyl, hydroxy,
halogen, cyano,
vitro, amino and C,-Cealkylamino, C,-Cedialkylamino, carboxy, C,-
CBalkoxycarbonyl,
C,_Cealkenyloxycarbonyl and C,-CBalkynyloxycarbonyl; or
R,5 is C4-C,2alkyl; C,-C,2halogenalkyl; C3-CBcycloalkyl; phenyl, naphthyl,
thienyl,
pyridyl, pyrimidinyl, triazinyl, or quinolyl with each of the aromatic ring
being optionally
substituted by 1 to 3 substituents selected from the group consisting of C,-
Cealkyl,
C2-Cealkenyl, wherein the hydrogens of all these substituents may be
optionally substituted
by one or more identical or different halogen atoms; C,-C$alkoxy, C,-
CBhalogenalkoxy,
C,-CBalkylthio, C,-Cehalogenalkylthio, halogen, cyano, vitro and C,-
Cealkoxycarbonyl; or
R,5 is C4-CBalkyl; C,-C6halogenalkyl; C3-CBcycloalkyl; phenyl, pyridyl, with
each of the
aromatic ring being optionally substituted by 1 to 3 substituents selected
from the group
consisting of C,-C$alkyl, C,-Cehalogenalkyl, C,-CBalkoxy, C,-Cehalogenalkoxy,
C,-Cgalkylthio, C,-Cehalogenalkylthio, halogen, cyano, vitro and C,-
Cealkoxycarbonyl; or
R,e is optionally substituted aryl or optionally substituted heteroaryl
consisting of one
or two condensed five or six membered rings with 1 to 4 identical or different
heteroatoms
selected from oxygen, nitrogen or sulfur; or
R,e is phenyl, naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl,
thiazolyl, oxazolyl,
isoxazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,
triazinyl, indolyl,
benzothiophenyl, benzofuranyl, benzimidazolyl, benzthiazolyl, benzoxazolyl or
quinolyl with
each of the aromatic ring being optionally substituted by 1 to 3 substituents
selected from
the group consisting of C,-Cealkyl, C2-Cealkenyl, C2-Cealkynyl, C3-
CBcycloalkyl,
C3-CBcycloalkyl-C,-C4alkyl, phenyl, phenyl-C,-C4alkyl wherein the hydrogens of
all these
substituents may be optionally substituted by one or more identical or
different halogen
atoms; C,-CBalkoxy, C3-Cealkenyloxy, C3-Cealkynyloxy, C,-CBalkoxy-C,-C4alkyl,
C,-Cehalogenalkoxy, C,-CBalkylthio, C,-Cehalogenalkylthio, C,-C$alkylsulfonyl,
formyl,
C2-Caalkanoyl, hydroxy, halogen, cyano, vitro, amino, C,-Cealkylamino, C,-
Cedialkylamino,
carboxy, C,-CBalkoxycarbonyl, C,~Cealkenyloxycarbonyl and C,-
Caalkynyloxycarbonyl; or
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
_7_
R,8 is phenyl, naphthyl, thienyl, pyridyl, pyrimidinyl, triazinyl, or quinolyl
with each of
the aromatic ring being optionally substituted by 1 to 3 substituents selected
from the group
consisting of C,-Cealkyl, C2-Cealkenyl, wherein the hydrogens of all these
substituents may
be optionally substituted by one or more identical or different halogen atoms;
C,-CBalkoxy,
C,-Cehalogenalkoxy, C,-Cealkylthio, C,-CBhalogenalkylthio, halogen, cyano,
vitro and
C,-Cealkoxycarbonyl; or
R,8 is phenyl, pyridyl, with each of the aromatic ring being optionally
substituted by
1 to 3 substituents selected from the group consisting of C,-Cealkyl, C,-
Cehalogenalkyl,
C,-Cealkoxy, C,-Cshalogenalkoxy, C,-Cealkylthio, C,-Cshalogenalkylthio,
halogen, cyano,
vitro and C,-Ce-alkoxycarbonyl; or
Z is oxygen, sulfur or -CH2- ; or
Z is oxygen.
Further preferred subgroups of the compounds of formula I are those wherein
1 ) R, is C,-C,2alkyl, C,-C,2alkyl substituted with C,-C4alkoxy, C,-
C4alkylthio, or
C,-C4alkylsulfonyl; C3-Cecycloalkyl; C2-C,2alkenyl; Cz-C,2alkynyl; C,-
C,2halogenalkyl; or a
group NR"R,2 wherein R" and R,2 are each independently of the other hydrogen
or
C,-Csalkyl, or together are tetra- or penta-methylene;
R2 is hydrogen and R3 is C,-Cealkyl; C,-CBalkyl substituted with hydroxy,
mercapto,
C,-C4alkoxy or C,-C4alkylthio; C3-Cealkenyl; C3-CBalkynyl; C3-Cecycloalkyl; C3-
C$cycloal-
kyl-C,-Caalkyl;
Ra is hydrogen, C,-Ce-alkyl, C2-CBalkenyl, C2-Cealkynyl, C3-CBCycloalkyl,
C3-Cecycloalkyl-C,-C4alkyl, C,-Cealkylthio, C,-CBalkylsulfonyl, C,-CBalkoxy,
C3-CBalkenyloxy,
C3-Cealkynyloxy, C3-CBCycloalkoxy, C,-CBalkoxy-C,-C4alkyl, C,-
Cealkoxycarbonyl,
C3-Cealkenyloxycarbonyl, C3-Cgalkynyloxycarbonyl, C,-Cgalkanoyl, C,-
CBdialkylamino,
C,-Cealkylamino wherein in each of the above radicals the alkyl, alkenyl,
alkynyl or
cycloalkyl groups may be partially or fully halogenated; carboxy, formyl,
halogen, vitro,
cyano, hydroxy or amino;
R9 is C,-CBalkyl, C2-Cealkenyl, C2-C$alkynyl, C3-Cecycloalkyl, C3-CBcyclo-
alkyl-C,-C4alkyl, C,-Cgalkylthio, C,-CBalkylsulfonyl, C,-Cealkoxy, C3-
Cgaikenyloxy,
C3-Cealkynyloxy, C3-Cscycloalkoxy, C,-Cealkoxy-C,-C4alkyl, C,-
Cealkoxycarbonyl,
C3-CBalkenyloxycarbonyl, C3-CBalkynyloxycarbonyl, C,-CBalkanoyl, C,-
CBdialkylamino,
C,-Cealkylamino wherein in each of the above radicals the alkyl, alkenyl,
alkynyl or
cycloalkyl groups may be partially or fully halogenated; carboxy, formyl,
halogen, vitro,
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
_g_
cyano, hydroxy or amino, provided that when Re is hydrogen, R9 is not C,-
Csalkoxy,
C3-Cfialkenyloxy or C3-Csalkynyloxy in position 3 of the phenyl ring carrying
these radicals ;
R,5 is C4-C,2alkyl; C,-C,2halogenalkyl; C3-Cecycloalkyl; optionally
substituted aryl or
optionally substituted heteroaryl consisting of one or two condensed five or
six membered
rings with 1 to 4 identical or different heteroatoms selected from oxygen,
nitrogen or sulfur;
and
R,e is optionally substituted aryl or optionally substituted heteroaryl
consisting of one
or two condensed five or six membered rings with 1 to 4 identical or different
heteroatoms
selected from oxygen, nitrogen or sulfur; or
2) n is one;
R, is C,-C,2alkyl, C2-C,2alkenyl; C,-C,Zhalogenalkyl; or a group NR"R,2
wherein R"
and R,2 are each independently of the other hydrogen or C,-Csalkyl;
R2 is hydrogen and R3 is C,-C4alkyl; C3-C4alkenyl or cyclopropyl;
R4 is hydrogen, methyl or ethyl;
RS , R6 and R, are each independently hydrogen or methyl; or
R8 is hydrogen, C,-Cealkyl, C,-CBhalogenalkyl, C2-CBalkenyl, C2-CBalkynyl,
C,-Cealkylthio, C,-CBhalogenalkylthio, C,-Cealkoxy, C,-CBhalogenalkoxy, C,-
Cealk-
oxy-C,-C4alkyl, C,-Cealkoxycarbonyl, C,-CBalkanoyl, formyl, halogen, nitro,
cyano or
hydroxy;
R9 is C,-C4alkyl, C,-C4halogenalkyl, C,-C4alkoxy, C,-C4alkoxycarbonyl, C,-
C4alkanoyl,
formyl, halogen, cyano or hydroxy, provided that when Re is hydrogen, R9 is
not C,-Csalkoxy
in position 3 of the phenyl ring carrying these radicals;
R,3, R,4, R,6, R,~ and R,9 are each independently hydrogen or methyl; or
R,5 is C4-C,2alkyl; C,-C,2halogenalkyl; C3-Cecycloalkyl; phenyl, naphthyl,
furyl, thienyl,
pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, thiazolyl,
pyridyl, pyridazinyl,
pyrimidinyl, pyrazinyl, triazinyl, indolyl, benzothiophenyl, benzofuranyl,
benzimidazolyl,
benzthiazolyl, benzoxazolyl or quinolyl with each of the aromatic ring being
optionally
substituted by 1 to 3 substituents selected from the group consisting of C,-
CBalkyl,
C2-CBalkenyl, C2-Caalkynyl, C3-C$cycloalkyl, C3-Cacycloalkyl-C,-C4alkyl,
phenyl,
phenyl-C,-C4alkyl wherein the hydrogens of all these substituents may be
optionally
substituted by one or more identical or different halogen atoms; C,-C-alkoxy,
C3-Cealken-
yloxy, C3-CBalkynyloxy, C,-Caalkoxy-C,-C4alkyl, C,-CBhalogenalkoxy, C,-
Caalkylthio,
C,-Cehalogenalkylthio, C,-Cealkylsulfonyl, formyl, C2-Ce-alkanoyl, hydroxy,
halogen, cyano,
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
_g_
nitro, amino, C,-CBalkylamino, C,-Cedialkylamino, carboxy, C,-
Cealkoxycarbonyl,
C,-Caalkenyloxycarbonyl and C,-Caalkynyloxycarbonyl;
R,8 is phenyl, naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl,
thiazolyl, oxazolyl,
isoxazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,
triazinyl, indolyl,
benzothiophenyl, benzofuranyl, benzimidazolyl, benzthiazolyl, benzoxazolyl or
quinolyl with
each of the aromatic ring being optionally substituted by 1 to 3 substituents
selected from
the group consisting of C,-CBalkyl, C2-Cealkenyl, C2-CBalkynyl, C3-
Cecycloalkyl,
C3-CBcycloalkyl-C,-C4alkyl, phenyl, phenyl-C,-C4alkyl wherein the hydrogens of
all these
substituents may be optionally substituted by one or more identical or
different halogen
atoms; C,-CBalkoxy, C3-Csalkenyloxy, C3-Cealkynyloxy, C,-Cealkoxy-C,-C4alkyl,
C,-Cahalogenalkoxy, C,-Csalkylthio, C,-Cehalogenalkylthio, C,-Cealkylsulfonyl,
formyl,
C2-Cealkanoyl, hydroxy, halogen, cyano, nitro, amino, C,-CBalkylamino, C,-
CBdialkylamino,
carboxy, C,-Cealkoxycarbonyl, C,_Cealkenyloxycarbonyl and C,-
Cealkynyloxycarbonyl; and
Z is oxygen, sulfur or -CH2- ; or
3) n is one;
R, is C,-Caalkyl, C2-C4alkenyl; C,-C4halogenalkyl; or C,-C2dialkylamino;
R2 is hydrogen and R3 is C3-C4alkyl; allyl or cyclopropyl;
R4 is hydrogen or methyl;
R5, R6, R,, R,3, R,4, R,6, R" and R,9 are each hydrogen;
R8 is hydrogen, C,-C4alkyl, C,-C4halogenalkyl, C,-C4alkoxy, C,-
C4alkoxycarbonyl,
C,-C4alkanoyl, formyl, halogen, cyano or hydroxy;
R9 is C,-C4alkyl, halogen or cyano;
R,5 is C4-C,2alkyl; C,-C,zhalogenalkyl; C3-CBcycloalkyl; phenyl, naphthyl,
thienyl,
pyridyl, pyrimidinyl, triazinyl, or quinolyl with each of the aromatic ring
being optionally
substituted by 1 to 3 substituents selected from the group consisting of C,-
Cealkyl,
C2-CBalkenyl, wherein the hydrogens of all these substituents may be
optionally substituted
by one or more identical or different halogen atoms; C,-CBalkoxy, C,-
CBhalogenalkoxy,
C,-CBalkylthio, C,-CBhalogenalkylthio, halogen, cyano, nitro and C,-
CBalkoxycarbonyl;
R,e is phenyl, naphthyl, thienyl, pyridyl, pyrimidinyl, triazinyl, or quinolyl
with each of
the aromatic ring being optionally substituted by 1 to 3 substituents selected
from the group
consisting of C,-C8-alkyl, C2-Cealkenyl, wherein the hydrogens of all these
substituents may
be optionally substituted by one or more identical or different halogen atoms;
C,-Cealkoxy,
C,-Cehalogenalkoxy, C,-C$alkylthio, C,-CBhalogenalkylthio, halogen, cyano,
nitro and
C,-C$alkoxycarbonyl; and
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-10
Z is oxygen, sulfur or -CH2- ; or
4) n is one;
R, is C,-C4alkyl, vinyl; C,-C4halogenalkyl; or dimethylamino;
R2 is hydrogen and R3 is isopropyl;
R4, R5, R,, R", R,2, R,4, R,5 and R" are each hydrogen;
RB is hydrogen;
R9 is C,-C4alkyl, halogen or cyano;
R,5 is C4-CBalkyl; C,-Cshalogenalkyl; C3-Cecycloalkyl; phenyl, pyridyl, with
each of the
aromatic ring being optionally substituted by 1 to 3 substituents selected
from the group
consisting of C,-Cealkyl, C,-Cehalogenalkyl, C,-Cealkoxy, C,-CBhalogenalkoxy,
C,-CBalkylthio, C,-Cehalogenalkylthio, halogen, cyano, nitro and C,-
CBalkoxycarbonyl;
R,e is phenyl, pyridyl, with each of the aromatic ring being optionally
substituted by
1 to 3 substituents selected from the group consisting of C,-CBalkyl, C,-
C$halogenalkyl,
C,-Cealkoxy, C,-C$halogenalkoxy, C,-Cealkylthio, C,-Cahalogenalkylthio,
halogen, cyano,
nitro and C,-C8-alkoxycarbonyl; and
Z is oxygen.
Preferred individual compounds are:
N-(2-{3-bromo-4-[3-(4-chloro-phenyl)-prop-2-ynyloxy]-5-methoxy-phenyl}-ethyl)-
2-
ethanesulfonylamino-3-methyl-butyramide,
N-(2-{3-bromo-4-[3-(4-bromo-phenyl)-prop-2-ynyloxy]-5-methoxy-phenyl}-ethyl)-2-
ethanesulfonylamino-3-methyl-butyramide,
N-(2-{3-bromo-4-[3-(4-fluoro-phenyl)-prop-2-ynyloxy]-5-methoxy-phenyl}-ethyl)-
2-
ethanesulfonylamino-3-methyl-butyramide,
N-{2-[3-bromo-4-(3-cyclopropyl-prop-2-ynyloxy)-5-methoxy-phenyl]-ethyl}-2-
ethanesulfonylamino-3-methyl-butyramide,
N-(2-{3-bromo-4-[3-(4-chloro-phenyl)-prop-2-ynyloxy]-5-methoxy-phenyl}-ethyl)-
2-
methanesulfonylamino-3-methyl-butyramide,
N-(2-{3-bromo-4-[3-(4-bromo-phenyl)-prop-2-ynyloxy]-5-methoxy-phenyl}-ethyl)-2-
methanesulfonylamino-3-methyl-butyramide,
N-(2-{3-bromo-4-[3-(4-fluoro-phenyl)-prop-2-ynyloxy]-5-methoxy-phenyl}-ethyl)-
2-
methanesulfonylamino-3-methyl-butyramide,
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-11
N-{2-[3-bromo-4-(3-cyclopropyl-prop-2-ynyloxy)-5-methoxy-phenyl)-ethyl}-2-
methanesulfonylamino-3-methyl-butyramide,
N-(2-{4-[3-(4-chloro-phenyl)-prop-2-ynyloxy]-3,5-dimethoxy-phenyl}-ethyl)-2-
ethanesulfonylamino-3-methyl-butyramide,
N-(2-{4-[3-(4-bromo-phenyl)-prop-2-ynyloxy)-3,5-dimethoxy-phenyl}-ethyl)-2-
ethanesulfonylamino-3-methyl-butyramide,
N-(2-{4-[3-(4-fluoro-phenyl)-prop-2-ynyloxy)-3,5-dimethoxy-phenyl}-ethyl)- 2-
ethanesulfonylamino-3-methyl-butyramide,
N-(2-{4-[3-(4-chloro-phenyl)-prop-2-ynyloxy)-3,5-dimethoxy-phenyl}-ethyl)-2-
methanesulfonylamino-3-methyl-butyramide,
N-(2-{4-[3-(4-bromo-phenyl)-prop-2-ynyloxy)-3,5-dimethoxy-phenyl}-ethyl)-2-
methanesulfonylamino-3-methyl-butyramide,
N-(2-{4-[3-(4-fluoro-phenyl)-prop-2-ynyloxy)-3,5-dimethoxy-phenyl}-ethyl)-2-
methanesulfonylamino-3-methyl-butyramide,
N-{2-[4-(3-cyclopropyl-prop-2-ynyloxy)-3,5-dimethoxy-phenyl)-ethyl}-2-
ethanesulfonylamino-
3-methyl-butyramide, and
N-{2-[4-(3-cyclopropyl-prop-2-ynyloxy)-3,5-dimethoxy-phenyl)-ethyl}-2-
methanesulfonylamino-3-methyl-butyramide.
Certain a-sulfin- and a-sulfonamino acid derivatives having a different kind
of structure have
already been proposed for controlling plant-destructive fungi (for example in
WO 95/030651, WO 97/14677, WO 98/38160 and WO 98/38161). The action of those
preparations is not, however, satisfactory in all aspects of agricultural
needs. Surprisingly,
with the compound structure of formula I, new kinds of microbicides having a
high level of
activity have been found.
The a-sulfin- and a-sulfonamino acid amides of formula I may be obtained
according to one
of the following processes:
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
_12_
a)
(~~)n
R2
R~ i °X + H2N-1-COOH
O V ~R3 IV
Step A
R
(~ ~ ~n R2 R4 R6 8
R' I H I OOH + HzN ~ ~ O R,o
O R3 II R5 R' R
III
Step B
( ~n Re
R2 O R4 R6
T
R' ~ H I H ' ~ ~ O R, o
O Rs Rs R~ R
9
An amino acid of formula If or a carboxy-activated derivative of an amino acid
of formula II
wherein R,, n, Rz and R3 are as defined for formula I is reacted with an amine
of formula III
wherein R4, R5, R6, R,, R8, Rg and R,o are as defined above optionally in the
presence of a
base and optionally in the presence of a diluting agent (step B).
Carboxy-activated derivatives of the amino acid of formula II encompasses all
compounds
having an activated carboxyl group like an acid halide, such as an acid
chloride, like
symmetrical or mixed anhydrides, such as mixed anhydrides with O-
alkylcarbonates, like
activated esters, such as p-nitrophenylesters or N-hydroxysuccinimidesters, as
well as in
situ produced activated forms of the amino acid of formula II by condensating
agents, such
as dicyclohexylcarbodiimide, carbonyldiimidazol, benzotriazol-1-yloxy-
tris(dimethylamino)-
phosphonium hexafluorophosphate, O-benzotriazol-1-yl N,N,N',N'-
bis(pentamethylene) -
uronium hexafluorophosphate, O-benzotriazol-1-yl N,N,N',N'-
bis(tetramethylene)uronium
hexafluorophosphate, O-benzotriazol-1-yl N,N,N',N'-tetramethyluronium
hexafluoro-
phosphate or benzotriazol-1-yloxy-tripyrrolidinophosphonium
hexafluorophosphate. The
mixed anhydrides of the amino acids of the formula II may be prepared by
reaction of an
amino acid of formula II with chloroformic acid esters like chloroformic acid
alkylesters, such
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-13
as ethyl chloroformate or isobutyl chloroformate, optionally in the presence
of an organic or
inorganic base like a tertiary amine, such as triethylamine, N,N-diisopropyl-
ethylamine,
pyridine, N-methyl-piperidine or N-methyl-morpholine.
The present reaction is preferably performed in an inert solvent like
aromatic, non-aromatic
or halogenated hydrocarbons, such as chlorohydrocarbons e.g. dichloromethane
or
toluene; ketones, e.g. acetone; esters, e.g. ethyl acetate; amides, e.g. N,N-
dimethyl-
formamide; nitrites e.g. acetonitrile; or ethers e.g. diethylether, tert-butyl-
methylether,
dioxane or tetrahydrofurane or water. It is also possible to use mixtures of
these solvents.
The reaction is preformed optionally in the presence of an organic or
inorganic base like a
tertiary amine, e.g. triethylamine, N,N-diisopropyl-ethylamine, pyridine, N-
methyl-piperidine
or N-methyl-morpholine, like a metal hydroxide or a metal carbonate,
preferentially an alkali
hydroxide or an alkali carbonate, such as lithium hydroxide, sodium hydroxide
or potassium
hydroxide at temperatures ranging from -80°C to +150°C,
preferentially at temperatures
ranging from -40°C to +40°C.
The compounds of formula II may be prepared by reaction of an amino acid of
formula IV
where R2 and R3 are as defined for formula I with a sulfonyl halide or a
sulfinyl halide of
formula V where R, and n have the same meanings as defined above and where X
is
halide, preferentially chlorine or bromine (step A).
The reaction may be performed in an inert solvent like aromatic, non-aromatic
or
halogenated hydrocarbons, such as chlorohydrocarbons, e.g. dichloromethane or
toluene;
ketones, e.g. acetone; esters, e.g. ethyl acetate; ethers, e.g. diethylether,
tert-butyl-
methylether, dioxane or tetrahydrofurane or water. It is also possible to use
mixtures of
these solvents. The reaction is performed optionally in the presence of an
organic or
inorganic base like a tertiary amine, such as triethylamine, N,N-diisopropyl-
ethylamine,
pyridine, N-methyl-piperidine or N-methyl-morpholine, like a metal hydroxide
or a metal
carbonate, preferentially an alkali hydroxide or an alkali carbonate, such as
lithium
hydroxide, sodium hydroxide or potassium hydroxide at temperatures ranging
from -80°C to
+150°C, preferentially at temperatures ranging from -40°C to
+40°C.
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-14
b)
( ) R8
Rz O RQ Rs
~ ~~ T
R~ S-X + H2f~J~H ~_~II O R,o
O V ~R3 Rs R' R
9
VI
Step C
( ) Rs
R2 O R4 R6
T
R' S H~H ~ ~ O R,o
O Rs Rs R~ R
s I
The compounds of formula I may also be prepared by reaction of an amino acid
derivative
of formula VI wherein R2, R3, R4, Rs, R6, R,, Re, R s and R,o are as defined
for formula I with
a sulfonyl halide or a sulfinyl halide of formula V wherein R, and n are as
defined for
formula I and X is halide, preferentially chlorine or bromine (step C). The
reaction is
performed in the same manner as described for step A.
c)
R
R2 O R4 R6 s
R' S H I H ~ ~ O H + Y-R,o
O R3 Rs R~ R VIII
s VII
Step D
( ) Ra
R2 O R4 R6
T
R' S H~H ~ ~ O R,o
O R3 Rs R~ R I
s
The compounds of formula I may also be prepared by reaction of a phenol of
formula VII
wherein R,, n, R2, R3, R4, Rs, R6, R,, R8 and Rs are as defined for formula I
with a compound
of formula VIII wherein R,o is as defined for formula I and Y is a leaving
group like a halide
such as a chloride or bromide or a sulfonic ester such as a tosylate, mesylate
or triflate
(step D).
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-15
The reaction may be performed in an inert solvent like aromatic, non-aromatic
or
halogenated hydrocarbons, such as chlorohydrocarbons e.g. dichloromethane or
toluene;
ketones e.g. acetone or 2-butanone; esters, e.g. ethyl acetate; ethers, e.g.
diethylether, tert-
butyl-methylether, dioxane or tetrahydrofurane, amides, e.g.
dimethylformamide, nitrites,
e.g. acetonitrile, alcohols, e.g. methanol, ethanol, isopropanol, n-butanol or
tert-butanol,
sulfoxides e.g. dimethylsulfoxide or water. It is also possible to use
mixtures of these
solvents. The reaction is performed optionally in the presence of an organic
or inorganic
base like a tertiary amine, such as triethylamine, N,N-diisopropyl-ethylamine,
pyridine,
N-methyl-piperidine or N-methyl-morpholine, like a metal hydroxide, a metal
carbonate or a
metal alkoxide, preferentially an alkali hydroxide, an alkali carbonate or an
alkali alkoxide,
such as lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium
carbonate,
potassium carbonate, sodium methoxide, potassium methoxide, sodium ethoxide,
potassium ethoxide, sodium tert-butoxide or potassium tert-butoxide at
temperatures
ranging from -80°C to +200°C, preferentially at temperatures
ranging from 0°C to +120°C.
d)
R
(II )n R2 O Ra Rs 8 Ri3
R' S H I H ~ ~ O H + Y - R~s
O R3 Rs R' R9 VII R,a Vllla
Step E
R
R2 O R4 Rs a R,s
R' S H I H ~ ~ O - R,s
O R3 Rs R~ R R~4 IX
s .
Step F
R
R2 O RQ Rs s R~s H
~ ~~ T
R~ S-N~H \ ~ O R~s la
O H ERs Rs R~ ~ R,a H
9
The compounds of formula la may also be prepared via formula IX wherein R,, n,
R2, R3, R4,
Rs, Rs, R,, R8, Rs, R,3, R,4 and R,s are defined for formula I by reacting of
a phenol of
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-16
formula VII wherein R,, n, R2, R3, R4, R5, R6, R~, Re and R9 are as defined
for formula I with a
compound of formula Vllla wherein R,3, R,4 and R,5 are as defined for formula
I and Y is a
leaving group like a halide such as a chloride or bromide or a sulfonic ester
such as a
tosylate, mesylate or triflate (step E).
The reaction is performed in the same manner as described for step D.
The compounds of formula la R,3, R,4 and R,5 is as defined for formula I may
be prepared
by reaction of compounds of formula IX with hydrogen.
The reaction is performed in a solvent like ethers, e.g. diethylether, dioxane
or
tetrahydrofuran, or like alcohols, e.g. methanol or ethanol, or water in the
presence of
transition metals or transition metal salts, e.g. nickel, cobalt, palladium,
platinium or
rhodium, optionally in the presence of bases, e.g. ammonia, or in the presence
of salts, e.g.
barium sulfate, at temperatures ranging from -20°C to +160°C and
at pressures ranging
from 1 to 200 bar.
aa) The intermediate amines of formula III may be obtained by one of the
following
processes
Procedure 1
NOZ
CHO
CHO /
/ step 1 R8 Rs step 2 / step 3
Re Rs ~ ~ R R ~ III
8 \ I 9
O
OH ~ O
XIX R,o XX ~ XXI
Rio
Procedure 2
R4 O R4 NOH
O
RQ
Rs R~ Rs R~ Rs R~
/ / / step 3
step step
1 4
R8 Rs RB Rs ~ III
Rs
~
R8
\ \ I
I
OH
XXII
R R XXIV
XXIII ,o
io
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-17-
Procedure 3
CN
OH CN
Rs R~
Rs R~ Rs R~
step 5 step 1 / step 3
/ ~ / ~ Ra Rs ~ III
Ra \ Rs Ra ~ Rs
O
OH XXV OH XXVI I XXVII
R, o
Procedure 4
COOK COOR COOH
R R Rn Rs Ra Rs
a s
R R Rs R~ Rs R~
s ' step 1 step 6 step 7
/ / III
R R R
R / Rs Re \ s a \ s
a ~ i
O O
OH XXVIII I XXIX I XXX
R,o R,o
Step 1 is the alkylation of a phenol with a compound of formula VIII. The
reaction is
performed in the same manner as described for procedure c).
Step 2 is the reaction of an aromatic aldehyde with nitromethane. This
reaction is performed
in a solvent like an organic carboxylic acids, e.g. acetic acid optionally in
the presence of
the ammonium salt of this carboxylic acid, e.g. ammonium acetate at
temperatures ranging
from 0°C to +200 °C.
Step 3 is the reduction of an unsaturated nitrogen-compound. This reaction is
performed in
a solvent like an ether, e.g. diethylether, dioxane or tetrahydrofuran, or an
alcohol, e.g.
methanol, ethanol or isopropanol, with borohydride, with a boron-complex, e.g.
the complex
of borohydride with tetrahyrofuran, with an alkaliborohydride, with an
alkalialuminiumhydride, e.g. lithiumaluminiumhydride, with aluminiumhydride,
with an
aluminiumalkoxyhydride or with hydrogen optionally in the presence of a
transition metal, a
transition metal salt or a transition metal complex, e.g. nickel, cobalt,
palladium, platinium or
rhodium at temperatures ranging from -50°C to +200°C.
Step 4 is the reaction of an aldehyde or a ketone of formula with
hydroxylamine or with a
salt of hydroxylamine. This reaction is performed in a solvent like an
alcohol, e.g. methanol,
ethanol or isopropanol, like an ether, e.g. diethylether, dioxane or
tetrahydrofuran, like an
amide, e.g. dimethylformamide, or in water or in a mixture of these solvents
optionally in the
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-18-
presence of an organic or inorganic base like a tertiary amine, e.g.
triethylamine, like a
heterocyclic compound containing nitrogen, e.g. pyridine, or like an
alkalicarbonate, e.g.
sodium carbonate or potassium carbonate, at temperatures ranging from -
20°C to +150°C.
Step 5 is the exchange of hydroxy by cyanide. This reaction is performed in an
organic
solvent like an amide, e.g. dimethylformamide using a metal cyanide like an
alkali cyanide,
e.g. sodium cyanide or potassium cyanide, at temperatures ranging from
0°C to +200°C.
Step 6 is the hydrolysis of an alkyl ester. This reaction is performed in a
solvent like an
alcohol, e.g. methanol, ethanol or isopropanol, like an ether, e.g.
diethylether, dioxane or
tetrahydrofuran, like a halogenated hydrocarbon, e.g. dichloromethane, or
water or in a
mixture of these solvents optionally in the presence of an alkali hydroxide,
e.g. lithium
hydroxide, sodium hydroxide or potassium hydroxide, or optionally in the
presence of an
acid, e.g. hydrogen chloride, sulfuric acid or trifluoroacetic acid at
temperatures ranging
from -20°C to +160°C.
Step 7 is the reaction of a carboxylic acid or the activated form of this
carboxylic acid with
hydrogen azide or an azide-salt. An activated form of a carboxylic acid can be
the acid
halogenide, e.g. acid chloride, a symmetric or a mixed anhydride. Azide-salts
can be alkali
azides, e.g. sodium azide. The reaction is performed in a solvent like a
hydrocarbon, e.g.
toluene or xylene, like a halogenated hydrocarbon, e.g. chloroform, like an
ether, e.g.
dioxane, like a ketone, e.g. acetone or 2-butanone, like an alcohol, e.g.
methanol, ethanol
or tert-butanol, or water or in a mixture of these solvents optionally in the
presence of an
acid like an inorganic acid, e.g. sulfuric acid or hydrogen chloride at
temperatures ranging
from -40°C to +200°C.
In a preferred form the compounds of formula XXVI are prepared starting from
compounds
of the formula XXV by applying step 5 and step 1 in the same pot.
bb) Amines of formula VI can be obtained by the following process
R$
O R2 R4 R6
R-O~HN~COOH + HN / \ OH
R3 R5 R~ Rs XXXIV
XXXIII ,
step 8
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-19-
O R O Ra R Ra
R-O~HN~HN s / \ OH
~R3 R5 R~
Rs
XXXV
+ VIII step 9
Ra
O R2 O Ra Rs
R-O~HN--~--~HN ~ ~ O-Rio
R3 R5 R~ R
s
step 10
VI
wherein R is lower alkyl or optionally substituted benzyl.
XXVI
Step 8 is the amidation of an carbamate-protected amino acid of formula XXXIII
with an
amine of formula XXXIV. The reaction is performed in the same manner as
described for
step A.
Step 9 is the alkylation of a phenol of formula XXXV with an compound of
formula VIII. The
reaction is performed in the same manner as described for step D.
Step 10 is the hydrolysis of a carbamate of formula XXXVI. The reaction is
performed in a
solvent like hydrocarbons, e.g. toluene, like halogenated hydrocarbons, e.g.
dichloromethane, like ketones, e.g. acetone, like esters, e.g. ethyl acetate,
like ethers, e.g.
dioxane or tetrahydrofuran, or like water or in mixtures of these solvents
optionally in the
presence of an organic acid like carboxylic acid, e.g. trifluoroacetic acid,
or like a sulfonic
acid, e.g. methanesulfonic acid or toluenesulfonic acid, or in the presence of
an inorganic
acid, e.g. hydrogen chloride or sulfuric acid, at temperatures ranging from -
40°C to +160°C.
The compounds of formula I are oils or solids at room temperature and are
distinguished by
valuable microbiocidal properties. They can be used in the agricultural sector
or related
fields preventively and curatively in the control of plant-destructive
microorganisms. The
compounds of formula I according to the invention are distinguished at low
rates of concen-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-20
tration not only by outstanding microbiocidal, especially fungicidal, activity
but also by being
especially well tolerated by plants.
Surprisingly, it has now been found that the compounds of formula I have for
practical
purposes a very advantageous biocidal spectrum in the control of
phytopathogenic micro-
organisms, especially fungi. They possess very advantageous curative and
preventive
properties and are used in the protection of numerous crop plants. With the
compounds of
formula I it is possible to inhibit or destroy phytopathogenic microorganisms
that occur on
various crops of useful plants or on parts of such plants (fruit, blossom,
leaves, stems,
tubers, roots), while parts of the plants which grow later also remain
protected, for example,
against phytopathogenic fungi.
The novel compounds of formula I prove to be effective against specific genera
of the
fungus class Fungi imperfecti (e.g. Cercospora), Basidiomycetes (e.g.
Puccinia) and
Ascomycetes (e.g. Erysiphe and Venturia) and especially against Oomycetes
(e.g.
Plasmopara, Peronospora, Pythium and Phytophthora). They therefore represent
in plant
protection a valuable addition to the compositions for controlling
phytopathogenic fungi. The
compounds of formula I can also be used as dressings for protecting seed
(fruit, tubers,
grains) and plant cuttings from fungal infections and against phytopathogenic
fungi that
occur in the soil.
The invention relates also to compositions comprising compounds of formula I
as active
ingredient, especially plant-protecting compositions, and to the use thereof
in the agri-
cultural sector or related fields.
In addition, the present invention includes the preparation of those
compositions, wherein
the active ingredient is homogeneously mixed with one or more of the
substances or groups
of substances described herein. Also included is a method of treating plants
which is distin-
guished by the application of the novel compounds of formula I or of the novel
compositions.
Target crops to be protected within the scope of this invention comprise, for
example, the
following species of plants: cereals (wheat, barley, rye, oats, rice, maize,
sorghum and
related species); beet (sugar beet and fodder beet); pomes, stone fruit and
soft fruit
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-21
(apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries
and black-
berries); leguminous plants (beans, lentils, peas, soybeans); oil plants
(rape, mustard,
poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans,
groundnuts); cucurbi-
taceae (marrows, cucumbers, melons); fibre plants (cotton, flax, hemp, jute);
citrus fruit
(oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce,
asparagus,
cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado,
cinnamon,
camphor) and plants such as tobacco, nuts, coffee, sugar cane, tea, pepper,
vines, hops,
bananas and natural rubber plants, and also ornamentals.
The compounds of formula I are normally used in the form of compositions and
can be
applied to the area or plant to be treated simultaneously or in succession
with other active
ingredients. Those other active ingredients may be fertilisers, micronutrient
donors or other
preparations that influence plant growth. It is also possible to use selective
herbicides or
insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures
of several of
those preparations, if desired together with further carriers, surfactants or
other application-
promoting adjuvants customarily employed in formulation technology.
The compounds of formula I can be mixed with other fungicides, resulting in
some cases in
unexpected synergistic activities.
Mixing components which are particularly preferred are azoles such as azoles,
such as
azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole,
diniconazole,
epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol,
hexaconazole,
imazalil, imibenconazole, ipconazole, metconazole, myclobutanil, pefurazoate,
penconazole, pyrifenox, prochloraz, propiconazole, tebuconazole,
tetraconazole,
triadimefon, triadimenol, triflumizole, triticonazole; pyrimidinyl carbinols,
such as ancymidol,
fenarimol, nuarimol; 2-amino-pyrimidines, such as bupirimate, dimethirimol,
ethirimol;
morpholines, such as dodemorph, fenpropidine, fenpropimorph, spiroxamine,
tridemorph;
anilinopyrimidines, such as cyprodinil, mepanipyrim, pyrimethanil;
pyrroles, such as fenpiclonil, fludioxonil; phenylamides, such as benalaxyl,
furalaxyl,
metalaxyl, R-metalaxyl, ofurace, oxadixyl; benzimidazoles, such as benomyl,
carbendazim,
debacarb, fuberidazole, thiabendazole; dicarboximides, such as chlozolinate,
dichlozoline,
iprodione, myclozoline, procymidone, vinclozolin; carboxamides, such as
carboxin,
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-22-
fenfuram, flutolanil, mepronil, oxycarboxin, thifluzamide; guanidines, such as
guazatine,
dodine, iminoctadine;
strobilurines, such as azoxystrobin, kresoxim-methyl, metominostrobin, SSF-
129,
CGA 279202 (trifloxystrobin), picoxystrobin; dithiocarbamates, such as ferbam,
mancozeb,
maneb, metiram, propineb, thiram, zineb, ziram; N-
halogenmethylthiophthalimides, such as
captafol, captan, dichlofluanid, fluoromide, folpet, tolyfluanid; Cu
compounds, such as
Bordeaux mixture, copper hydroxide, copper oxychloride, copper sulfate,
cuprous oxide,
mancopper, oxine-copper; nitrophenol derivatives, such as dinocap, nitrothal-
isopropyl;
organo-P derivatives, such as edifenphos, iprobenphos, isoprothiolane,
phosdiphen,
pyrazophos, tolclofos-methyl; various, such as AC 382042, acibenzolar-S-
methyl, anilazine,
blasticidin-S, quinomethionat, chloroneb, chlorothalonil, cymoxanil, dichlone,
diclomezine,
dicloran, diethofencarb, dimethomorph, dithianon, etridiazole, famoxadone,
fenamidone,
fenhexamid, fentin, ferimzone, fluazinam, flusulfamide, fosetyl-aluminium,
hymexazol, IKF-
916, iprovalicarb, kasugamycin, methasulfocarb, MON65500, pencycuron,
phthalide,
polyoxins, probenazole, propamocarb, pyroquilon, quinoxyfen, quintozene, RH-
7281,
RPA 407213, BAS 50001 F, sulfur, SYP-2071, triazoxide, tricyclazole,
triforine, validamycin.
Suitable carriers and surfactants may be solid or liquid and correspond to the
substances
ordinarily employed in formulation technology, such as e.g. natural or
regenerated mineral
substances, solvents, dispersants, wetting agents, tackifiers, thickeners,
binders or
fertilisers. Such carriers and additives are described, for example, in WO
95/30651.
A preferred method of applying a compound of formula I, or an agrochemical
composition
comprising at least one of those compounds, is application to the foliage
(foliar application),
the frequency and the rate of application depending upon the risk of
infestation by the
pathogen in question. The compounds of formula I may also be applied to seed
grains
(coating) either by impregnating the grains with a liquid formulation of the
active ingredient
or by coating them with a solid formulation.
The compounds of formula I are used in unmodified form or, preferably,
together with the
adjuvants conventionally employed in formulation technology, and are for that
purpose
advantageously formulated in known manner e.g. into emulsifiable concentrates,
coatable
pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable
powders, soluble
powders, dusts, granules, and by encapsulation in e.g. polymer substances. As
with the
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
- 23 -
nature of the compositions, the methods of application, such as spraying,
atomising,
dusting, scattering, coating or pouring, are chosen in accordance with the
intended object-
ives and the prevailing circumstances
Advantageous rates of application are normally from 1 g to 2 kg of active
ingredient (a.i.)
per hectare (ha), preferably from 10 g to 1 kg a.i.lha, especially from 25 g
to 750 g a.i./ha.
When used as seed dressings, rates of from 0.001 g to 1.0 g of active
ingredient per kg of
seed are advantageously used.
The formulations, i.e. the compositions, preparations or mixtures comprising
the com-
pounds) (active ingredient(s)) of formula I and, where appropriate, a solid or
liquid
adjuvant, are prepared in known manner, e.g. by homogeneously mixing and/or
grinding the
active ingredient with extenders, e.g. solvents, solid carriers and, where
appropriate,
surface-active compounds (surfactants).
Further surfactants customarily used in formulation technology will be known
to the person
skilled in the art or can be found in the relevant technical literature.
The agrochemical compositions usually comprise 0.01 to 99 % by weight,
preferably 0.1 to
95 % by weight, of a compound of formula I, 99.99 to 1 % by weight, preferably
99.9 to 5
by weight, of a solid or liquid adjuvant, and 0 to 25 % by weight, preferably
0.1 to 25 % by
weight, of a surfactant.
Whereas commercial products will preferably be formulated as concentrates, the
end user
will normally employ dilute formulations.
The compositions may also comprise further ingredients, such as stabilisers,
antifoams,
viscosity regulators, binders and tackifiers, as well as fertilisers or other
active ingredients
for obtaining special effects.
The Examples which follow illustrate the invention described above, without
limiting the
scope thereof in any way. Temperatures are given in degrees Celsius.
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-24-
Preparation Examples for compounds of formula I
xam~le A1.1 : ~S)-N-(2- 3-Bromo-4-f3-L4-chloro-phenyl)-prop-2-ynyloxyl-5-
methoxy-phenyl)-
ethyl)-2-ethanesulfonylamino-3-methyl-butyramide
Br
o - ~ ~ ci
O H O
N' ~
H3C~ISOI V 'H-CH2 CHZ ~ O.
CH3
H3C~CH3
A mixture of (S)-N-[2-(3-bromo-4-hydroxy-5-methoxy-phenyl)-ethyl]-2-
ethanesulfonylamino-
3-methyl-butyramide (1.5 g), toluene-4-sulfonic acid 3-(4-chloro-phenyl)-prop-
2-ynyl ester
(1.7 g) and sodium methoxide (6.5 ml, 1 M solution in methanol) in methanol
(40 ml) is
heated to reflux for 2 hours. After cooling water (500 ml) is added. The
mixture is extracted
with ethyl acetate (2 x 500 ml). The organic layers are washed with brine (2 x
100 ml),
combined, dried (MgSOa) and the solvent is evaporated. (S)-N-(2-(3-Bromo-4-[3-
(4-chloro-
phenyl)-prop-2-ynyloxy]-5-methoxy-phenyl}-ethyl)-2-ethanesulfonylamino-3-
methyl-
butyramide is obtained and is purified by flash-column chromatography on
silica gel (ethyl
acetate/hexane) and recrystallization (ethyl acetate/hexane), m.p. 109-111
°C.
Analogously to example A1.1 the compounds listed in table A1 are obtained.
*) Configuration on the a-C-atom in the amino acid moiety ; Ph means phenyl
Table A1
O H O R4 H Ra
T
R' ISI H~H ~ ~ O R,o
O R3 H H
R9
No R, *) R3 R4 R8 ~ R9 R,o m.p. (C)
A1.1 CH3-CHz- (S) (CH3)2CH-H 3-OCH3 5- (4-CI-Ph)-C=C-CHz-109-111
Br
A1.2 CH3-CH2- (S) (CH3)2CH-H 3-OCH3 5- (3,4-di-CI-Ph)-CH2-148-150
Br
A1.3 CH3- (S) (CH3)2CH-H 2-OCH3 H (4-CI-Ph)-C---C-CHZ-129-130
A1.4 CH3- (S) (CH3)2CH-H 2-OCH3 H (4-Br-Ph)-C=C-CH2-133-135
'I
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
- 25 -
A1.5 CH3- (S) (CH3)2CH-H 3-CI H (4-CI-Ph)-C---C-CH2-156-157
A1.6 CH3- (S) (CH3)2CH-H 3-CI H (4-Br-Ph)-C=C-CH2-155-156
A1.7 CH3-CH2- (S) (CH3)2CH-H 3-Br H (4-CI-Ph)-C---C-CH2-147-149
A1.8 CH3-CH2- (S) (CH3)zCH-H 3-Br H (4-CH3-Ph)-C---C-CH2-124-126
Example A2.1. : ~ )-N-[2-(3-Bromo-4-h rLdroxy-5-methoxy-phenyl -ether]-2-
ethanesulfonylamino-3-methyl-butyramide
Br
O
O~ -N~ ~ OH
H3CUj N-CH2 CH2
O H O-CH3
H3C~CH3
(S)-N-[2-(4-Benzyloxy-3-bromo-5-methoxy-phenyl)-ethyl]-2-ethanesulfonylamino-3-
methyl-
butyramide (11.7 g) and palladium (3.6 g, 5% on charcoal) in tetrahydrofuran
(200 ml) are
shaken under a hydrogen atmosphere at +20 to +22°C and at normal
pressure for 30
hours. The reaction mixture is filtered and evaporated. (S)-N-[2-(3-Bromo-4-
hydroxy-5-
methoxy-phenyl)-ethyl]-2-ethanesulfonylamino-3-methyl-butyramide is obtained,
and is
purified by flash-column chromatography on silica gel (ethyl acetate/hexane)
and
recrystallization (ethyl acetate/hexane), m.p. 145-147°C.
Analogously to example A2.1 the compounds listed in table A2 are obtained.
*) Configuration on the a-C-atom in the amino acid moiety
Table A2
O H p R4 H Re
T'
R' ISI H ~ H ~ ~ O H
O R3 H H
R9
No R, *) R3 R4 R8 R9 m.p. (C)
A2.1 CH3-CH2- (S) (CH3)2CH- H 3-OCH3 Br 145-147
A2.2 CH3- (S) (CH3)zCH- H 2-OCH3 H 123-125
A2.3 CH3- (S) (CH3)2CH- H 3-CI H 146-151
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-26
Example A3.1: (SLN-f2-(4-Benz~y-3-bromo-5-methox~pheny~-eth~J-2-
ethanesulfonylamino-3-methyl-bu~ramide
Br
H3C~S~N~ / / O
'N-CH2 CHZ ~
H O-CH3
H3C~CH3
To (S)-2-Ethanesulfonylamino-3-methyl-butyric acid (15.6 g), 2-(4-benzyloxy-3-
bromo-5-
methoxy-phenyl)-ethylamine (25 g) and N,N-diisopropylethylamine (27 ml) in N,N-
Dimethyl-
formamide (300 ml) is added benzotriazol-1-yloxytris(dimethylamino)phosphonium
hexafluorophosphate (36.2 g) in one portion. The reaction mixture is stirred
at room
temperature for 4 hours. Water (1 I) is then added. The mixture is extracted
with ethyl
acetate (2 x 500 ml). The organic layers are washed with brine (2 x 100 ml),
combined,
dried (MgS04) and the solvent is evaporated. (S)-N-[2-(4-Benzyloxy-3-bromo-5-
methoxy-
phenyl)-ethyl]-2-ethanesulfonylamino-3-methyl-butyramide is obtained, and is
purified by
flash-column chromatography on silica gel (ethyl acetate/hexane) and
recrystallization (ethyl
acetate/hexane), m.p. 128-130°C.
Analogously to example A3.1 the compounds listed in table A3 are obtained.
*) Configuration on the a.-C-atom in the amino acid moiety ; Ph means phenyl
Table A3
R8
O H O RQ H
_ _
R' II H~H ~ ~ O
O R3 H H
s
No R, *) R3 R4 R8 Rs m.p. (C)
3.1. CH3-CH2- (S) (CH3)2CH- H 3-OCH3 5-Br 141-152
3.2. CH3-CH2- (S) (CH3)2CH- H Ph-CH2- H 165-167
3.3. (CH3)2N- (S) (CH3)2CH- H Ph-CH2- H 108-109
3.4. CH3- (S) (CH3)2CH- H 2-OCH3 H 168-169
3.5. CH3- (S) (CH3)2CH- H 3-CI H 178-179
CA 02403563 2002-09-19
WO 01/79159 PCT/EPOI/04202
-27
Analogously to the above Examples the following compounds of Tables 1 to 16
may be
prepared. In the tables Ph means phenyl.
Table 1 : Compounds represented by the Formula 1.1 wherein the combination of
the
groups R,, R3 and R,o corresponds to each row in table A.
O
0
R~ S-N-~-~-N-CH2 CH2 ~ ~ O-Rio 1.1
O H R H
3
CH3
Table 2 : Compounds represented by the Formula 1.2 wherein the combination of
the
groups R,, R3 and R,o corresponds to each row in table A.
0
0
R~ S-N--~-~-N-CH2 CH2 ~ ~ O-Rio 1.2
O H R H
3
Table 3 : Compounds represented by the Formula 1.3 wherein the combination of
the
groups R,, R3 and R,o corresponds to each row in table A.
o
0
R~ S-N~-~-N-CH2 CH2 ~ ~ O-Rio 1.3
O H R H
3
F
Table 4 : Compounds represented by the Formula 1.4 wherein the combination of
the
groups R,, R3 and R,o corresponds to each row in table A.
O-CH3
O
O
R~ S-N~-~-N-CH2 CHZ ~ ~ O-Rio 1.4
O H R H
3
O -C H3
Table 5 : Compounds represented by the Formula 1.5 wherein the combination of
the
groups R,, R3 and R,o corresponds to each row in table A.
O-CH3
O
O
R~ S-N~N-CH2 CH2 ~ ~ O-R,o 1.5
O H R H
3
Br
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-28-
Table 6 : Compounds represented by the Formula 1.6 wherein the combination of
the
groups R,, R3 and R,o corresponds to each row in table A.
CH3
O
O
R~ S-N---~-N-CH2 CH2 ~ ~ O-Rio 1.6
O H R H
3
CH3
Table 7 : Compounds represented by the Formula 1.7 wherein the combination of
the
groups R,, R3 and R,o corresponds to each row in table A.
0
0
R~ S-N-r~N-CH2 CH2 ~ ~ O-Rio
H H
O R3 1.7
H3C-O
Table 8 : Compounds represented by the Formula 1.8 wherein the combination of
the
groups R,, R3 and R,o corresponds to each row in table A.
Br
0
0
R~ S-N~-N-CH2 CH2 ~ ~ O-Rio L8
O H R H
3
Br
Table 9 : Compounds represented by the Formula 1.9 wherein the combination of
the
groups R,, R3 and R,o corresponds to each row in table A.
ci
0
0
R~ S-N-~N-CH2 CH2 ~ ~ O-R~o 1.9
O H R H
3
C~
Table 10 : Compounds represented by the Formula 1.10 wherein the combination
of the
groups R,, R3 and R,o corresponds to each row in table A.
O-CH3
O
O
R~ S-N---~-N-CHZ CH2 ~ ~ O-Rio 1.10
H R H
3
Br
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
- 29 -
Table 11 : Compounds represented by the Formula 1.11 wherein the combination
of the
groups R,, R3 and R,o corresponds to each row in table A.
O-CH3
O O CH3
R~ S-H-~H-CH-CHz ~ ~ O-Rio 1.11
O Rs
Br
Table A
No. R, R3 R,o
001 CH3- CH3-CH2- CH3-(CH2)3-C---C-CH2-
002 CH3-CH2- CH3-CH2- CH3-(CH2)3-C-C-CH2-
003 (CH3)2N- CH3-CH2- CH3-(CH2)3-C-C-CH2-
004 CH3-CH2-CH2- CH3-CH2- CH3-(CH2)3-C-C-CH2-
005 (CH3)2CH- CH3-CH2- CH3-(CH2)3-C---C-CH2-
006 CI-CH2-CH2-CH2-CH3-CH2- CH3-(CHz)3-C-C-CH2-
007 CH3- (CH3)2CH- CH3-(CH2)3-C---C-CH2-
008 CH3-CH2- (CH3)2CH- CH3-(CH2)3-C=C-CH2-
009 (CH3)2N- (CH3)2CH- CH3-(CH2)3-C-C-CH2-
010 CH3-CH2-CH2- (CH3)2CH- CH3-(CH2)3-C-C-CH2-
011 (CH3)2CH- (CH3)2CH- CH3-(CH2)3-C-C-CH2-
012 CI-CH2-CH2-CH2-(CH3)2CH- CH3-(CH2)3-C=C-CH2-
013 CH3- CH3-CH2-CH2- CH3-(CHz)3-C-C-CH2-
014 CH3-CH2- CH3-CH2-CH2- CH3-(CH2)3-C---C-CHz-
015 (CH3)2N- CH3-CH2-CH2- CH3-(CH2)3-C=C-CH2-
016 CH3-CH2-CH2- CH3-CH2-CHz- CH3-(CH2)3-C-C-CH2-
017 (CH3)2CH- CH3-CH2-CHz- CH3-(CH2)3-C=C-CH2-
018 CI-CH2-CH2-CH2-CH3-CHz-CH2- CH3-(CH2)3-C-C-CH2-
019 CH3- CCH- CHs-(CH2)3-C=C-CH2_
020 CH3-CH2- CCH- CHs-(CH2)3-C---C-CH2-
021 (CHs)zN- CCH- CH3-(CHz)s-C=C-CH2_
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-30-
022 CH3-CH2-CH2- CCH- CH3-(CHz)s-C-C-CH2_
023 (CH3)2CH- CCH- CH3-(CH2)3-C-C-CHz_
024 CI-CH2-CH2-CH2-CCH- CH3-(CH2)3-C-C-CH2-
025 CH3- CH2=CH-CH2- CH3-(CH2)3-C-C-CHz-
026 CH3-CHz- CH2=CH-CH2- CH3-(CH2)3-C-C-CH2-
027 (CH3)2N- CH2=CH-CH2- CH3-(CH2)3-C---C-CH2-
028 CH3-CH2-CH2- CH2=CH-CH2- CH3-(CH2)3-C---C-CH2-
029 (CH3)2CH- CH2=CH-CH2- CH3-(CH2)3-C---C-CH2-
030 CI-CH2-CH2-CH2-CH2=CH-CH2- CH3-(CH2)3-C-C-CH2-
031 CH3- CH---C-CH2- CH3-(CHZ)3-C---C-CH2-
032 CH3-CH2- CH---C-CH2- CH3-(CH2)3-C---C-CH2-
033 (CH3)2N- CH--_C-CH2- CH3-(CH2)3-C-C-CH2-
034 CH3-CH2-CH2- CH--__C-CH2- CH3-(CHz)3-C-C-CH2-
035 (CH3)2CH- CH=C-CH2- CH3-(CH2)3-C-C-CH2-
036 CI-CH2-CH2-CH2-CH=C-CH2- CH3-(CH2)3-C---C-CH2-
037 CH3- CH3-CH2-CH(CH3)-CH3-(CH2)3-C---C-CH2-
038 CH3-CH2- CH3-CH2-CH(CH3)-CH3-(CHZ)3-C=C-CH2-
039 (CH3)2N- CH3-CH2-CH(CH3)-CH3-(CH2)3-C---C-CH2-
040 CH3-CH2-CH2- CH3-CH2-CH(CH3)-CH3-(CH2)3-C---C-CH2-
041 (CH3)2CH- CH3-CH2-CH(CH3)-CH3-(CH2)3-C---C-CH2-
042 CI-CH2-CH2-CH2-CH3-CH2-CH(CH3)-CH3-(CH2)3-C---C-CH2-
045 CH3- CH3-CH2- ~CH2-
046 CH3-CH2- CH3-CH2- ~CH2-
047 (CH3)2N- CH3-CH2- ~CH2-
048 CH3-CH2-CHz- CH3-CH2- ~-CH2-
049 (CH3)2CH- CH3-CH2- ~CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-31
050 CI-CH2-CH2-CH2-CH3-CH2- ~CH2-
51 CH3- (CH3)2CH- ~CH2-
052 CH3-CH2- (CH3)2CH- ~CH2-
053 (CH3)2N- (CH3)2CH-
~-CH2-
054 CH3-CH2-CH2- (CH3)2CH- ~CHz-
055 (CH3)2CH- (CH3)2CH- ~CHz-
056 CI-CH2-CH2-CH2-(CH3)2CH- ~-CH2-
057 CH3- CH3-CH2-CH2- ~CH2-
058 CH3-CH2- CH3-CH2-CH2- ~CH2-
059 (CH3)ZN- CH3-CH2-CH2- ~CH2-
060 CH3-CH2-CH2- CH3-CH2-CH2- ~CH2-
061 (CH3)2CH- CH3-CH2-CH2-
DCH2-
062 CI-CH2-CH2-CH2-CH3-CH2-CHz- ~CH2-
063 CH3- CCH- DCH2-
064 CH3-CH2- CCH- DCH2-
065 (CH3)2N- CCH- ~CH2_
066 CH3-CH2-CH2- CCH- ~CH2_
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-32
067 (CHs)zCH- CCH- ~CH2_
068 CI-CH2-CH2-CH2-CCH- ~-CH2-
069 CH3- CH2=CH-CH2- ~CH2-
070 CH3-CH2- CH2=CH-CH2- ~CH2-
071 (CH3)2N- CH2=CH-CH2- ~CH2-
072 CH3-CH2-CH2- CH2=CH-CH2-
~CH2_
073 (CH3)2CH- CH2=CH-CH2- ~CHz-
074 CI-CH2-CHZ-CH2-CH2=CH-CHz-
-- =CH2-
075 CH3- CH--_C-CH2- ~CHz-
076 CH3-CH2- CH--__C-CH2- ~CH2-
077 (CH3)2N- CH-_-_-C-CH2- ~CH2-
078 CH3-CH2-CH2- CH-_-_-C-CH2- ~CH2-
079 (CH3)2CH- CH=C-CH2- ~CH2-
080 CI-CH2-CH2-CH2-CH---C-CH2- ~CH2-
081 CH3- CH3-CH2-CH(CH3)-~CH2-
082 CH3-CH2- CH3-CH2-CH(CH3)-
~CH2_
083 (CH3)2N- CH3-CH2-CH(CH3)-
DC H2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
- 33 -
084 CH3-CH2-CH2- CH3-CH2-CH(CH3)-
DC H2-
085 (CH3)2CH- CH3-CH2-CH(CH3)-
D-C H2-
086 CI-CH2-CH2-CH2-CH3-CH2-CH(CH3)-~CH2-
087 CH3- CH3-CH2- Ph-C---C-CH2-
088 CH3-CH2- CH3-CH2- Ph-C---C-CH2-
089 (CH3)2N- CH3-CH2- Ph-C---C-CH2-
090 CH3-CH2-CH2- CH3-CH2- Ph-C--__C-CHz-
091 (CH3)2CH- CH3-CH2- Ph-C---C-CH2-
092 CI-CH2-CH2-CH2-CH3-CH2- Ph-C---C-CH2-
093 CH3- (CH3)2CH- Ph-C---C-CH2-
094 CH3-CH2- (CH3)2CH- Ph-C---C-CH2-
095 (CH3)2N- (CH3)ZCH- Ph-C--__C-CH2-
096 CH3-CH2-CH2- (CH3)2CH- Ph-C--__C-CH2-
097 (CH3)2CH- (CH3)2CH- Ph-C=C-CH2-
098 CI-CH2-CH2-CH2-(CH3)2CH- Ph-C=C-CH2-
099 CH3- CH3-CH2-CH2- Ph-C---C-CH2-
100 CH3-CH2- CH3-CH2-CH2- Ph-C=C-CH2-
101 (CH3)2N- CH3-CH2-CH2- Ph-C--__C-CH2-
102 CH3-CH2-CH2- CH3-CH2-CH2- Ph-C--__C-CH2-
103 (CH3)2CH- CH3-CH2-CH2- Ph-C=C-CH2-
104 CI-CH2-CH2-CHz-CH3-CH2-CH2- Ph-C---C-CH2-
105 CH3- CCH- Ph-C--_C-CH2-
106 CH3-CH2- CCH- Ph-C--_C-CH2-
107 (CH3)2N- CCH- Ph-C---C-CH2-
108 CH3-CH2-CH2- CCH- Ph-C---C-CH2-
109 (CH3)2CH- CCH- Ph-C---C-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-34-
110 CI-CH2-CH2-CH2-CCH- Ph-C--__C-CH2-
111 CH3- CH2=CH-CH2- Ph-C--__C-CH2-
112 CH3-CH2- CH2=CH-CH2- Ph-C--__C-CH2-
113 (CH3)2N- CH2=CH-CH2- Ph-C---C-CH2-
114 CH3-CH2-CH2- CH2=CH-CH2- Ph-C--__C-CH2-
115 (CH3)2CH- CH2=CH-CH2- Ph-C---C-CH2-
116 CI-CH2-CH2-CH2-CH2=CH-CH2- Ph-C-_-C-CH2-
117 CH3- CH--_C-CH2- Ph-C--__C-CH2-
118 CH3-CH2- CH=C-CH2- Ph-C=C-CH2-
119 (CH3)2N- CH---C-CH2- Ph-C=C-CH2-
120 CH3-CH2-CH2- CH=C-CH2- Ph-C--__C-CH2-
121 (CH3)2CH- CH--__C-CH2- Ph-C--__C-CHz-
122 CI-CH2-CH2-CHz-CH---C-CH2- Ph-C=C-CH2-
123 CH3- CH3-CH2-CH(CH3)-Ph-C---C-CH2-
124 CH3-CH2- CH3-CH2-CH(CH3)-Ph-C---C-CH2-
125 (CH3)2N- CH3-CH2-CH(CH3)-Ph-C=C-CH2-
126 CH3-CH2-CH2- CH3-CH2-CH(CH3)-Ph-C=C-CH2-
127 (CH3)2CH- CH3-CH2-CH(CH3)-Ph-C--__C-CH2-
128 CI-CH2-CH2-CH2-CH3-CH2-CH(CH3)-Ph-C-_-C-CH2-
129 CH3- CH3-CHz- (4-F-Ph)-C---C-CH2-
130 CH3-CH2- CH3-CH2- (4-F-Ph)-C_--C-CH2-
131 (CH3)2N- CH3-CH2- (4-F-Ph)-C---C-CH2-
132 CH3-CH2-CH2- CH3-CH2- (4-F-Ph)-C--__C-CH2-
133 (CH3)2CH- CH3-CH2- (4-F-Ph)-C--__C-CH2-
134 CI-CH2-CH2-CH2-CH3-CH2- (4-F-Ph)-C---C-CH2-
135 CH3- (CH3)2CH- (4-F-Ph)-C-_-C-CH2-
136 CH3-CH2- (CH3)2CH- (4-F-Ph)-C---C-CH2-
137 (CH3)2N- (CH3)2CH- (4-F-Ph)-C---C-CH2-
138 CH3-CH2-CH2- (CH3)2CH- (4-F-Ph)-C---C-CH2-
139 (CH3)2CH- (CH3)2CH- (4-F-Ph)-C=C-CH2-
140 CI-CH2-CH2-CH2-(CH3)2CH- (4-F-Ph)-C---C-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPOi/04202
- 35 -
141 CH3- CH3-CH2-CH2- (4-F-Ph)-C--__C-CH2-
142 CH3-CH2- CH3-CH2-CH2- (4-F-Ph)-C-_-C-CH2-
143 (CH3)2N- CH3-CH2-CH2- (4-F-Ph)-C---C-CH2-
144 CH3-CH2-CH2- CH3-CH2-CH2- (4-F-Ph)-C---C-CH2-
145 (CH3)2CH- CH3-CH2-CH2- (4-F-Ph)-C=C-CH2-
146 CI-CH2-CH2-CH2-CH3-CH2-CH2- (4-F-Ph)-C-_-C-CH2-
147 CH3- CCH- (4-F-Ph)-C--_C-CH2-
148 CH3-CH2- CCH- (4-F-Ph)-C--__C-CH2-
149 (CH3)2N- CCH- (4-F-Ph)-C--__C-CHZ-
150 CH3-CH2-CH2- CCH- (4-F-Ph)-C---C-CH2-
151 (CH3)2CH- CCH- (4-F-Ph)-C--_C-CH2-
152 CI-CH2-CH2-CH2-CCH- (4-F-Ph)-C--_C-CH2-
153 CH3- CH2=CH-CH2- (4-F-Ph)-C---C-CH2-
154 CH3-CH2- CH2=CH-CH2- (4-F-Ph)-C=C-CH2-
155 (CH3)2N- CH2=CH-CH2- (4-F-Ph)-C--__C-CH2-
156 CH3-CH2-CH2- CH2=CH-CH2- (4-F-Ph)-C--__C-CH2-
157 (CH3)2CH- CH2=CH-CH2- (4-F-Ph)-C=C-CH2-
158 CI-CH2-CH2-CH2-CH2=CH-CH2- (4-F-Ph)-C--__C-CH2-
159 CH3- CH=C-CH2- (4-F-Ph)-C--__C-CH2-
160 CH3-CH2- CH--_C-CH2- (4-F-Ph)-C--__C-CH2-
161 (CH3)2N- CH-_-_-C-CH2- (4-F-Ph)-C=C-CH2-
162 CH3-CHz-CHZ- CH-C-CH2- (4-F-Ph)-C--_C-CH2-
163 (CH3)2CH- CH_--C-CH2- (4-F-Ph)-C--_C-CH2-
164 CI-CH2-CH2-CH2-CH---C-CH2- (4-F-Ph)-C---C-CH2-
165 CH3- CH3-CH2-CH(CH3)-(4-F-Ph)-C--__C-CH2-
166 CH3-CH2- CH3-CH2-CH(CH3)-(4-F-Ph)-C=C-CH2-
167 (CH3)2N- CH3-CH2-CH(CH3)-(4-F-Ph)-C---C-CH2-
168 CH3-CH2-CH2- CH3-CH2-CH(CH3)-(4-F-Ph)-C---C-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-36
169 (CH3)2CH- CH3-CH2-CH(CH3)-(4-F-Ph)-C---C-CH2-
170 CI-CH2-CH2-CH2-CH3-CH2-CH(CH3)-(4-F-Ph)-C--__C-CH2-
171 CH3- CH3-CH2- (4-CI-Ph)-C---C-CHz-
172 CH3-CH2- CH3-CH2- (4-CI-Ph)-C---C-CH2-
173 (CH3)2N- CH3-CH2- (4-CI-Ph)-C=C-CH2-
174 CH3-CH2-CH2- CH3-CH2- (4-CI-Ph)-C--__C-CH2-
175 (CH3)2CH- CH3-CH2- (4-CI-Ph)-C--_C-CHZ-
176 CI-CH2-CH2-CH2-CH3-CH2- (4-CI-Ph)-C=C-CH2-
177 CH3- (CH3)zCH- (4-CI-Ph)-C-_-C-CH2-
178 CH3-CH2- (CH3)2CH- (4-CI-Ph)-C--__C-CH2-
179 (CH3)2N- (CH3)2CH- (4-CI-Ph)-C---C-CH2-
180 CH3-CH2-CH2- (CH3)2CH- (4-CI-Ph)-C---C-CH2-
181 (CH3)2CH- (CH3)zCH- (4-CI-Ph)-C--__C-CH2-
182 CI-CH2-CH2-CH2-(CH3)2CH- (4-CI-Ph)-C---C-CH2-
183 CH3- CH3-CH2-CH2- (4-CI-Ph)-C---C-CH2-
184 CH3-CH2- CH3-CH2-CH2- (4-CI-Ph)-C=C-CH2-
185 (CH3)2N- CH3-CH2-CH2- (4-CI-Ph)-C=C-CHZ-
186 CH3-CH2-CH2- CH3-CH2-CH2- (4-CI-Ph)-C---C-CH2-
187 (CH3)2CH- CH3-CH2-CH2- (4-CI-Ph)-C--__C-CH2-
188 CI-CH2-CH2-CH2-CH3-CH2-CH2- (4-CI-Ph)-C--__C-CH2-
189 CH3- CCH- (4-CI-Ph)-C--__C-CH2-
190 CH3-CH2- CCH- (4-CI-Ph)-C---C-CH2-
191 (CH3)2N- CCH- (4-CI-Ph)-C-_-C-CH2-
192 CH3-CH2-CH2- CCH- (4-CI-Ph)-C---C-CH2-
193 (CH3)2CH- CCH- (4-CI-Ph)-C=C-CH2-
194 CI-CH2-CH2-CH2-CCH- (4-CI-Ph)-C=C-CH2-
195 CH3- CH2=CH-CH2- (4-CI-Ph)-C=C-CH2-
196 CH3-CH2- CH2=CH-CH2- (4-CI-Ph)-C-_-C-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-37-
197 (CH3)2N- CH2=CH-CH2- (4-CI-Ph)-C--__C-CH2-
198 CH3-CH2-CHz- CH2=CH-CH2- (4-CI-Ph)-C--__C-CH2-
199 (CH3)2CH- CH2=CH-CH2- (4-CI-Ph)-C=C-CH2-
200 CI-CHz-CH2-CH2-CH2=CH-CH2- (4-CI-Ph)-C=C-CH2-
201 CH3- CH=C-CH2- (4-CI-Ph)-C---C-CH2-
202 CH3-CH2- CH=C-CH2- (4-CI-Ph)-C_--C-CH2-
203 (CH3)2N- CH--__C-CH2- (4-CI-Ph)-C---C-CH2-
204 CH3-CH2-CH2- CH--_C-CH2- (4-CI-Ph)-C--__C-CH2-
205 (CH3)2CH- CH--_C-CH2- (4-CI-Ph)-C=C-CH2-
206 CI-CH2-CH2-CH2-CH--_C-CH2- (4-CI-Ph)-C---C-CH2-
207 CH3- CH3-CH2-CH(CH3)-(4-CI-Ph)-C---C-CH2-
208 CH3-CH2- CH3-CH2-CH(CH3)-(4-CI-Ph)-C---C-CH2-
209 (CH3)2N- CH3-CH2-CH(CH3)-(4-CI-Ph)-C=C-CH2-
210 CH3-CH2-CH2- CH3-CH2-CH(CH3)-(4-CI-Ph)-C--__C-CH2-
211 (CH3)2CH- CH3-CH2-CH(CH3)-(4-CI-Ph)-C--__C-CH2-
212 CI-CH2-CH2-CH2-CH3-CH2-CH(CH3)-(4-CI-Ph)-C--__C-CH2-
213 CH3- CH3-CH2- (4-Br-Ph)-C---C-CHZ-
214 CH3-CH2- CH3-CH2- (4-Br-Ph)-C-C-CH2-
215 (CH3)2N- CH3-CH2- (4-Br-Ph)-C---C-CH2-
216 CH3-CH2-CH2- CH3-CH2- (4-Br-Ph)-C--__C-CH2-
217 (CH3)2CH- CH3-CH2- (4-Br-Ph)-C--__C-CH2-
218 CI-CH2-CH2-CH2-CH3-CH2- (4-Br-Ph)-C=C-CH2-
219 CH3- (CH3)2CH- (4-Br-Ph)-C=C-CH2-
220 CH3-CH2- (CH3)2CH- (4-Br-Ph)-C---C-CH2-
221 (CH3)2N- (CH3)2CH- (4-Br-Ph)-C---C-CH2-
222 CH3-CH2-CH2- (CH3)2CH- (4-Br-Ph)-C--__C-CH2-
223 (CH3)ZCH- (CH3)2CH- (4-Br-Ph)-C=C-CH2-
224 CI-CH2-CH2-CH2-(CH3)2CH- (4-Br-Ph)-C--__C-CH2-
225 CH3- CH3-CH2-CH2- (4-Br-Ph)-C---C-CH2-
226 CH3-CH2- CH3-CH2-CH2- (4-Br-Ph)-C---C-CH2-
227 (CH3)zN- CH3-CH2-CH2- (4-Br-Ph)-C--__C-CH2-
228 CH3-CH2-CH2- CH3-CH2-CH2- (4-Br-Ph)-C--__C-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-38-
229 (CH3)2CH- CH3-CH2-CH2- (4-Br-Ph)-C=C-CH2-
230 CI-CH2-CH2-CH2-CH3-CH2-CH2- (4-Br-Ph)-C--_C-CH2-
231 CH3- CCH- (4-Br-Ph)-C---C-CH2-
232 CH3-CH2- CCH- (4-Br-Ph)-C---C-CH2-
233 (CH3)2N- CCH- (4-Br-Ph)-C--_C-CH2-
234 CH3-CH2-CH2- CCH- (4-Br-Ph)-C=C-CH2-
235 (CH3)2CH- (4-Br-Ph)-C---C-CH2-
CCH-
236 CI-CH2-CH2-CH2-CCH- (4-Br-Ph)-C---C-CHz-
237 CH3- CH2=CH-CH2- (4-Br-Ph)-C---C-CH2-
238 CH3-CH2- CH2=CH-CH2- (4-Br-Ph)-C=C-CH2-
239 (CH3)2N- CH2=CH-CH2- (4-Br-Ph)-C--_C-CHz-
240 CH3-CHZ-CH2- CH2=CH-CH2- (4-Br-Ph)-C=C-CH2-
241 (CH3)2CH- CH2=CH-CH2- (4-Br-Ph)-C--__C-CH2-
242 CI-CH2-CH2-CH2-CH2=CH-CH2- (4-Br-Ph)-C---C-CH2-
243 CH3- CH=C-CH2- (4-Br-Ph)-C--_C-CH2-
244 CH3-CH2- CH--_C-CH2- (4-Br-Ph)-C=C-CH2-
245 (CH3)2N- CH--_C-CH2- (4-Br-Ph)-C=C-CH2-
246 CH3-CH2-CH2- CH--_C-CH2- (4-Br-Ph)-C--_C-CH2-
247 (CH3)2CH- CH--_C-CH2- (4-Br-Ph)-C--__C-CH2-
248 CI-CH2-CH2-CH2-CH--_C-CHz- (4-Br-Ph)-C--__C-CH2-
249 CH3- CH3-CH2-CH(CH3)-(4-Br-Ph)-C--__C-CH2-
250 CH3-CH2- CH3-CH2-CH(CH3)-(4-Br-Ph)-C--_C-CH2-
251 (CH3)2N- CH3-CH2-CH(CH3)-(4-Br-Ph)-C=C-CH2-
252 CH3-CH2-CH2- CH3-CH2-CH(CH3)-(4-Br-Ph)-C--_C-CH2-
253 (CH3)2CH- CH3-CH2-CH(CH3)-(4-Br-Ph)-C--__C-CH2-
254 CI-CH2-CH2-CH2-CH3-CH2-CH(CH3)-(4-Br-Ph)-C---C-CHZ-
255 CH3- CH3-CH2- H
256 CH3-CH2- CH3-CH2- H
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-39-
257 (CH3)2N- CH3-CH2- H
258 CH3-CH2-CH2- CH3-CH2- H
259 (CH3)2CH- CH3-CHz- H
260 CI-CH2-CH2-CH2-CH3-CH2- H
261 CH3- (CH3)2CH- H
262 CH3-CH2- (CH3)2CH- H
263 (CH3)2N- (CH3)2CH- H
264 CH3-CH2-CH2- (CH3)2CH- H
265 (CH3)ZCH- (CH3)2CH- H
266 CI-CH2-CH2-CHZ-(CH3)2CH- H
267 CH3- CH3-CH2-CH2- H
268 CH3-CH2- CH3-CH2-CH2- H
269 (CH3)2N- CH3-CH2-CH2- H
270 CH3-CH2-CH2- CH3-CH2-CH2- H
271 (CH3)2CH- CH3-CH2-CH2- H
272 CI-CH2-CH2-CH2-CH3-CH2-CH2- H
273 CH3- CCH- H
274 CH3-CH2- CCH- H
275 (CH3)2N- CCH- H
276 CH3-CH2-CH2- CCH- H
277 (CH3)2CH- CCH- H
278 CI-CH2-CH2-CH2-CCH- H
279 CH3- CH2=CH-CH2- H
280 CH3-CH2- CH2=CH-CH2- H
281 (CH3)2N- CH2=CH-CH2- H
282 CH3-CH2-CH2- CH2=CH-CH2- H
283 (CH3)2CH- CH2=CH-CH2- H
284 CI-CH2-CH2-CH2-CH2=CH-CH2- H
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-40-
285 CH3- CH--__C-CH2- H
286 CH3-CH2- CH--__C-CH2- H
287 (CH3)2N- CH--__C-CH2- H
288 CH3-CH2-CH2- CH--__C-CH2- H
289 (CH3)2CH- CH=C-CH2- H
290 CI-CH2-CH2-CH2-CH=C-CH2- H
291 CH3- CH3-CH2-CH(CH3)-H
292 CH3-CH2- CH3-CH2-CH(CH3)-H
293 (CH3)2N- CH3-CH2-CH(CH3)-H
294 CH3-CH2-CH2- CH3-CH2-CH(CH3)-H
295 (CH3)2CH- CH3-CH2-CH(CH3)-H
296 CI-CH2-CH2-CH2-CH3-CH2-CH(CH3)-H
297 CH3- CH3-CH2- Ph-CH2-
298 CH3-CH2- CH3-CH2- Ph-CH2-
299 (CH3)2N- CH3-CH2- Ph-CH2-
300 CH3-CH2-CH2- CH3-CH2- Ph-CH2-
301 (CH3)2CH- CH3-CH2- Ph-CH2-
302 CI-CH2-CH2-CH2-CH3-CH2- Ph-CH2-
303 CH3- (CH3)2CH- Ph-CH2-
304 CH3-CH2- (CH3)zCH- Ph-CH2-
305 (CH3)2N- (CH3)2CH- Ph-CH2-
306 CH3-CH2-CH2- (CH3)2CH- Ph-CH2-
307 (CH3)2CH- (CH3)2CH- Ph-CH2-
308 CI-CH2-CH2-CH2-(CH3)2CH- Ph-CH2-
309 CH3- CH3-CH2-CH2- Ph-CH2-
310 CH3-CH2- CH3-CH2-CH2- Ph-CH2-
311 (CH3)2N- CH3-CH2-CH2- Ph-CH2-
312 CH3-CH2-CH2- CH3-CH2-CH2- Ph-CH2-
313 (CH3)2CH- CH3-CH2-CH2- Ph-CH2-
314 CI-CH2-CH2-CH2-CH3-CH2-CH2- Ph-CH2-
315 CH3- ~CH- Ph-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-41 -
316 CH3-CH2- CCH- Ph-CH2-
317 (CH3)2N- CCH- Ph-CH2-
318 CH3-CH2-CH2- CCH- Ph-CH2-
319 (CH3)2CH- CCH- Ph-CH2-
320 CI-CH2-CH2-CH2-CCH- Ph-CH2-
321 CH3- CH2=CH-CH2- Ph-CH2-
322 CH3-CH2- CH2=CH-CH2- Ph-CH2-
323 (CH3)2N- CH2=CH-CHZ- Ph-CH2-
324 CH3-CH2-CHz- CH2=CH-CHz- Ph-CH2-
325 (CH3)2CH- CH2=CH-CH2- Ph-CH2-
326 CI-CH2-CH2-CHz-CH2=CH-CH2- Ph-CH2-
327 CH3- CH--__C-CH2- Ph-CH2-
328 CH3-CH2- CH--__C-CH2- Ph-CH2-
329 (CH3)2N- CH--__C-CH2- Ph-CHz-
330 CH3-CH2-CH2- CH--__C-CH2- Ph-CH2-
331 (CH3)2CH- CH---C-CH2- Ph-CH2-
332 CI-CH2-CH2-CH2-CH=C-CH2- Ph-CH2-
333 CH3- CH3-CH2-CH(CH3)-Ph-CH2-
334 CH3-CH2- CH3-CH2-CH(CH3)-Ph-CH2-
335 (CH3)2N- CH3-CH2-CH(CH3)-Ph-CH2-
336 CH3-CH2-CH2- CH3-CH2-CH(CH3)-Ph-CH2-
337 (CH3)2CH- CH3-CHz-CH(CH3)-Ph-CH2-
338 CI-CH2-CH2-CH2-CH3-CH2-CH(CH3)-Ph-CH2-
339 CH3- CH3-CH2- (4-CI-Ph)-CHz-
340 CH3-CH2- CH3-CH2- (4-CI-Ph)-CH2-
341 (CH3)2N- CH3-CH2- (4-CI-Ph)-CH2-
342 CH3-CH2-CH2- CH3-CH2- (4-CI-Ph)-CHz-
343 (CH3)2CH- CH3-CH2- (4-CI-Ph)-CH2-
344 CI-CH2-CH2-CH2-CH3-CH2- (4-CI-Ph)-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-42-
345 CH3- (CH3)2CH- (4-CI-Ph)-CH2-
346 CH3-CH2- (CH3)2CH- (4-CI-Ph)-CH2-
347 (CH3)2N- (CH3)2CH- (4-CI-Ph)-CH2-
348 CH3-CH2-CH2- (CH3)zCH- (4-CI-Ph)-CH2-
349 (CH3)2CH- (CH3)2CH- (4-CI-Ph)-CH2-
350 CI-CH2-CH2-CH2-(CH3)2CH- (4-CI-Ph)-CH2-
351 CH3- CH3-CH2-CH2- (4-CI-Ph)-CH2-
352 CH3-CH2- CH3-CHz-CH2- (4-CI-Ph)-CH2-
353 (CH3)2N- CH3-CH2-CH2- (4-CI-Ph)-CH2-
354 CH3-CH2-CH2- CH3-CH2-CH2- (4-CI-Ph)-CH2-
355 (CH3)2CH- CH3-CH2-CH2- (4-CI-Ph)-CH2-
356 CI-CH2-CH2-CH2-CH3-CH2-CH2- (4-CI-Ph)-CH2-
357 CH3- CCH- (4-CI-Ph)-CH2-
358 CH3-CH2- ~CH- (4-CI-Ph)-CH2-
359 (CH3)2N- CCH- (4-CI-Ph)-CH2-
360 CH3-CH2-CH2- CCH- (4-CI-Ph)-CH2-
361 (CH3)2CH- CCH- (4-CI-Ph)-CHz-
362 CI-CH2-CH2-CHz-CCH- (4-CI-Ph)-CH2-
363 CH3- CH2=CH-CH2- (4-CI-Ph)-CH2-
364 CH3-CH2- CH2=CH-CH2- (4-CI-Ph)-CH2-
365 (CH3)2N- CH2=CH-CH2- (4-CI-Ph)-CH2-
366 CH3-CH2-CH2- CH2=CH-CH2- (4-CI-Ph)-CH2-
367 (CH3)2CH- CH2=CH-CH2- (4-CI-Ph)-CH2-
368 CI-CH2-CH2-CH2-CH2=CH-CH2- (4-CI-Ph)-CH2-
369 CH3- CH---C-CH2- (4-CI-Ph)-CH2-
370 CH3-CH2- CH=C-CH2- (4-CI-Ph)-CH2-
371 (CH3)2N- CH=C-CH2- (4-CI-Ph)-CH2-
372 CH3-CH2-CH2- CH--__C-CH2- (4-CI-Ph)-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
- 43 -
373 (CH3)2CH- CH---C-CHz- (4-CI-Ph)-CH2-
374 CI-CH2-CH2-CH2-CH---C-CH2- (4-CI-Ph)-CH2-
375 CH3- CH3-CH2-CH(CH3)-(4-CI-Ph)-CH2-
376 CH3-CH2- CH3-CH2-CH(CH3)-(4-CI-Ph)-CH2-
378 (CH3)2N- CH3-CH2-CH(CH3)-(4-CI-Ph)-CH2-
379 CH3-CH2-CHz- CH3-CH2-CH(CH3)-(4-CI-Ph)-CH2-
380 (CH3)2CH- CH3-CH2-CH(CH3)-(4-CI-Ph)-CH2-
381 CI-CH2-CH2-CH2-CH3-CHz-CH(CH3)-(4-CI-Ph)-CH2-
382 CH3- CH3-CH2- (3-CI-Ph)-CH2-
383 CH3-CH2- CH3-CH2- (3-CI-Ph)-CH2-
384 (CH3)2N- CH3-CH2- (3-CI-Ph)-CH2-
385 CH3-CH2-CH2- CH3-CH2- (3-CI-Ph)-CH2-
386 (CH3)2CH- CH3-CHZ- (3-CI-Ph)-CH2-
387 CI-CH2-CH2-CH2-CH3-CH2- (3-CI-Ph)-CH2-
388 CH3- (CH3)2CH- (3-CI-Ph)-CH2-
389 CH3-CH2- (CH3)2CH- (3-CI-Ph)-CH2-
390 (CH3)2N- (CH3)ZCH- (3-CI-Ph)-CH2-
391 CH3-CH2-CH2- (CH3)2CH- (3-CI-Ph)-CH2-
392 (CH3)2CH- (CH3)2CH- (3-CI-Ph)-CH2-
393 CI-CH2-CH2-CH2-(CH3)2CH- (3-CI-Ph)-CH2-
394 CH3- CH3-CH2-CH2- (3-CI-Ph)-CH2-
395 CH3-CHZ- CH3-CH2-CH2- (3-CI-Ph)-CH2-
396 (CH3)2N- CH3-CH2-CH2- (3-CI-Ph)-CH2-
397 CH3-CH2-CH2- CH3-CH2-CH2- (3-CI-Ph)-CH2-
398 (CH3)2CH- CH3-CH2-CH2- (3-CI-Ph)-CH2-
399 CI-CH2-CH2-CH2-CH3-CH2-CH2- (3-CI-Ph)-CH2-
400 CH3- CCH- (3-CI-Ph)-CH2-
401 CH3-CH2- CCH- (3-CI-Ph)-CH2-
402 (CH3)2N- CCH- (3-CI-Ph)-CH2-
403 CH3-CH2-CH2- CCH- (3-CI-Ph)-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-44-
404 (CH3)2CH- CCH- (3-CI-Ph)-CH2-
405 CI-CH2-CH2-CH2-CCH- (3-CI-Ph)-CH2-
406 CH3- CH2=CH-CH2- (3-CI-Ph)-CH2-
407 CH3-CH2- CH2=CH-CH2- (3-CI-Ph)-CH2-
408 (CH3)2N- CH2=CH-CH2- (3-CI-Ph)-CH2-
409 CH3-CH2-CH2- CH2=CH-CH2- (3-CI-Ph)-CH2-
410 (CH3)zCH- CH2=CH-CH2- (3-CI-Ph)-CH2-
411 CI-CH2-CH2-CH2-CH2=CH-CH2- (3-CI-Ph)-CH2-
412 CH3- CH--__C-CH2- (3-CI-Ph)-CHz-
413 CH3-CH2- CH=C-CH2- (3-CI-Ph)-CH2-
414 (CH3)2N- CH---C-CH2- (3-CI-Ph)-CH2-
415 CH3-CH2-CH2- CH--__C-CH2- (3-CI-Ph)-CH2-
416 (CH3)2CH- CH--__C-CH2- (3-CI-Ph)-CH2-
417 CI-CH2-CH2-CH2-CH=C-CH2- (3-CI-Ph)-CH2-
418 CH3- CH3-CH2-CH(CH3)-(3-CI-Ph)-CH2-
419 CH3-CH2- CH3-CH2-CH(CH3)-(3-CI-Ph)-CHz-
420 (CH3)2N- CH3-CH2-CH(CH3)-(3-CI-Ph)-CH2-
421 CH3-CH2-CH2- CH3-CH2-CH(CH3)-(3-CI-Ph)-CH2-
422 (CH3)2CH- CH3-CHz-CH(CH3)-(3-CI-Ph)-CH2-
423 CI-CH2-CH2-CH2-CH3-CH2-CH(CH3)-(3-CI-Ph)-CH2-
424 CH3- CH3-CH2- (3-CF3-Ph)-CH2-
425 CH3-CH2- CH3-CH2- (3-CF3-Ph)-CHz-
426 (CH3)2N- CH3-CH2- (3-CF3-Ph)-CH2-
427 CH3-CH2-CH2- CH3-CH2- (3-CF3-Ph)-CH2-
428 (CH3)2CH- CH3-CH2- (3-CF3-Ph)-CH2-
429 CI-CH2-CH2-CH2-CH3-CH2- (3-CF3-Ph)-CH2-
430 CH3- (CH3)2CH- (3-CF3-Ph)-CH2-
431 CH3-CH2- (CH3)2CH- (3-CF3-Ph)-CHz-
432 (CH3)2N- (CH3)2CH- (3-CF3-Ph)-CH2-
433 CH3-CH2-CH2- (CH3)2CH- (3-CF3-Ph)-CH2-
434 (CH3)2CH- (CH3)2CH- (3-CF3-Ph)-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-45-
435 CI-CH2-CH2-CH2-(CH3)2CH- (3-CF3-Ph)-CH2-
436 CH3- CH3-CH2-CH2- (3-CF3-Ph)-CH2-
437 CH3-CH2- CH3-CH2-CHZ- (3-CF3-Ph)-CH2-
438 (CH3)2N- CH3-CH2-CH2- (3-CF3-Ph)-CH2-
439 CH3-CH2-CHz- CH3-CH2-CHz- (3-CF3-Ph)-CH2-
440 (CH3)2CH- CH3-CH2-CH2- (3-CF3-Ph)-CH2-
441 CI-CH2-CH2-CHZ-CH3-CH2-CH2- (3-CF3-Ph)-CH2-
442 CH3- CCH- (3-CF3-Ph)-CH2-
443 CH3-CH2- CCH- (3-CF3-Ph)-CH2-
444 (CH3)2N- CCH- (3-CF3-Ph)-CH2-
445 CH3-CH2-CH2- CCH- (3-CF3-Ph)-CH2-
446 (CH3)2CH- CCH- (3-CF3-Ph)-CH2-
447 CI-CH2-CH2-CH2-CCH- (3-CF3-Ph)-CH2-
448 CH3- CH2=CH-CH2- (3-CF3-Ph)-CH2-
449 CH3-CH2- CH2=CH-CH2- (3-CF3-Ph)-CH2-
450 (CH3)2N- CH2=CH-CH2- (3-CF3-Ph)-CHz-
451 CH3-CH2-CH2- CH2=CH-CH2- (3-CF3-Ph)-CH2-
452 (CH3)2CH- CH2=CH-CH2- (3-CF3-Ph)-CH2-
453 CI-CH2-CH2-CH2-CH2=CH-CH2- (3-CF3-Ph)-CHZ-
454 CH3- CH--__C-CHz- (3-CF3-Ph)-CH2-
455 CH3-CH2- CH--__C-CH2- (3-CF3-Ph)-CH2-
456 (CH3)2N- CH=C-CH2- (3-CF3-Ph)-CH2-
457 CH3-CH2-CH2- CH=C-CH2- (3-CF3-Ph)-CH2-
458 (CH3)2CH- CH---C-CH2- (3-CF3-Ph)-CH2-
459 CI-CH2-CH2-CH2-CH--__C-CH2- (3-CF3-Ph)-CH2-
460 CH3- CH3-CH2-CH(CH3)-(3-CF3-Ph)-CH2-
461 CH3-CH2- CH3-CH2-CH(CH3)-(3-CF3-Ph)-CH2-
462 (CH3)zN- CH3-CH2-CH(CH3)-(3-CF3-Ph)-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-46-
463 CH3-CH2-CH2- CH3-CH2-CH(CH3)-(3-CF3-Ph)-CH2-
464 (CH3)2CH- CH3-CH2-CH(CH3)-(3-CF3-Ph)-CH2-
465 CI-CH2-CH2-CH2-CH3-CH2-CH(CH3)-(3-CF3-Ph)-CH2-
Table 12 : Compounds represented by the Formula 1.12 where the combination of
the
groups R, and R3 corresponds to each row in table B.
O-CH3
O
O
R~ S-H~H-CH2 CH2 ~ ~ O CH2 ~ ~ G 1.12
O R3
Br
Table 13 : Compounds represented by the Formula 1.13 where the combination of
the
groups R, and R3 corresponds to each row in table B.
O-CH3
O
O
R~ S-H--,-~LH-CHZ CH2 ~ ~ O-CH2 ~ ~ Br 1.13
O R3
Br
Table 14 : Compounds represented by the Formula 1.14 where the combination of
the
groups R, and R3 corresponds to each row in table B.
O-CH3
O
O
R; S-H--~-~H-CH2 CH2 ~ ~ O-CH2 ~ ~ F 1.14
O R3
Br
Table B
No. R, R3
001 (CH3-CH2)2N- CH3-CHz-
002 CH3-CH2-(CH3)N- CH3-CH2-
003 - CH3-CH2-
N
004 CH3- (CH2)2-CH2- CH3-CH2-
005 (CH3)2CH-CH2- CH3-CH2-
006 CH3-CH2-(CH3)CH- CH3-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-47-
007 (CH3)3C- CH3-CH2-
008 CH2=CH- CH3-CH2-
009 CH3-CH2-
CCH-
010 (CH3-CH2)2N- (CH3)2CH-
011 CH3-CH2-(CH3)N- (CH3)2CH-
012 - (CH3)2CH-
N
013 CH3-(CH2)2-CH2- (CH3)ZCH-
014 (CH3)2CH-CH2- (CH3)2CH-
015 CH3-CH2-(CH3)CH- (CH3)zCH-
016 (CH3)3C- (CH3)2CH-
017 CH2=CH- (CH3)2CH-
018 (CH3)2CH-
CCH-
019 (CH3-CH2)2N- CH3-CH2-CH2
020 CH3-CH2-(CH3)N- CH3-CH2-CH2
021 _ CH3-CH2-CH2
N
022 CH3-(CH2)2-CH2- CH3-CH2-CH2
023 (CH3)2CH-CH2- CH3-CH2-CH2
024 CH3-CH2-(CH3)CH- CH3-CH2-CH2
025 (CH3)3C- CH3-CH2-CH2
026 CH2=CH- CH3-CH2-CH2
027 CH3-CH2-CH2
CCH-
028 (CH3-CH2)2N- CH3-CH2-(CH3)CH-
029 CH3-CH2-(CH3)N- CH3-CH2-(CH3)CH-
030 - CH3-CH2-(CH3)CH-
N
031 CH3-(CH2)2-CHz- CH3-CH2-(CH3)CH-
032 (CH3)2CH-CH2- CH3-CH2-(CH3)CH-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-48-
033 CH3-CH2-(CH3)CH- CH3-CH2-(CH3)CH-
034 (CH3)3C- CH3-CH2-(CH3)CH-
035 CH2=CH- CH3-CH2-(CH3)CH-
036 CH3-CH2-(CH3)CH-
CCH-
037 (CH3-CH2)2N- CCH-
038 CH3-CH2-(CH3)N- CCH-
039 - CCH-
N
040 CH3-(CH2)2-CH2- CCH-
041 (CH3)2CH-CH2- CCH-
042 CH3-CH2-(CH3)CH- CCH-
043 (CH3)3C- CCH-
044 CH2=CH- CCH-
045 CCH-
CCH-
046 CH3- HO-CH2-
047 CH3-CH2- HO-CH2-
048 (CH3)2N- HO-CH2-
049 CH3-CH2-CH2- HO-CH2-
050 (CH3)2CH- HO-CH2-
051 CH3-CH2-(CH3)CH- HO-CH2-
052 CH3- HO-(CH3)CH-
053 CH3-CH2- HO-(CH3)CH-
054 (CH3)2N- HO-(CH3)CH-
055 CH3-CH2-CH2- HO-(CH3)CH-
056 (CH3)2CH- HO-(CH3)CH-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-49-
057 CH3-CH2-(CH3)CH- HO-(CH3)CH-
058 CH3- (CH3)3C-O-(CH3)CH-
059 CH3-CH2- (CH3)3C-O-(CH3)CH-
060 (CH3)2N- (CH3)3C-O-(CH3)CH-
061 CH3-CH2-CH2- (CH3)3C-O-(CH3)CH-
062 (CH3)2CH- (CH3)3C-O-(CH3)CH-
063 CH3-CH2-(CH3)CH- (CH3)3C-O-(CH3)CH-
064 CH3- CH3-S-CH2-CH2-
065 CH3-CH2- CH3-S-CH2-CH2-
066 (CH3)2N- CH3-S-CH2-CHz-
067 CH3-CH2-CH2- CH3-S-CH2-CH2-
068 (CH3)2CH- CH3-S-CH2-CH2-
069 CH3-CH2-(CH3)CH- CH3-S-CH2-CH2-
070 CH3- HS-CH2-CH2-
071 CH3-CH2- HS-CH2-CH2-
072 (CH3)2N- HS-CHZ-CH2-
073 CH3-CH2-CH2- HS-CH2-CH2-
074 (CH3)2CH- HS-CH2-CH2-
075 CH3-CH2-(CH3)CH- HS-CH2-CHZ-
076 CH3- (CH3)3C-
077 CH3-CH2- (CH3)3C-
078 (CH3)2N- (CH3)3C-
079 CH3-CH2-CHZ- (CH3)3C-
080 (CH3)2CH- (CH3)3C-
081 CH3-CH2-(CH3)CH- (CH3)3C-
Table 15 : Compounds represented by the Formula 1.15 where the combination of
the group
R,o corresponds to each row in table C.
O-CH3
O
O
H3C-S-H~H-CH2 CH2 O-R,o 1.15
O R3
O -CH3
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-50-
Table 16 : Compounds represented by the Formula 1.16 where the combination of
the group
R,o corresponds to each row in table C.
O-CH3
O
O
H3C-S-N--~-N-CH2 CH2 ~ ~ O-Rio 1.16
O H R H
3
Br
Table C
No. R,o
001 C H 3-C H 2-C ( C H 3) H-C---C-C H 2-
002 (CH3)3C-C--__C-CH2-
003 (CH3)2CH-CH2-C-C-CH2-
004 CH3-(CH2)4-C---C-CH2-
005
CH2
006
- CHZ
007 (4-CH3-Ph)-C--__C-CH2-
008 (2-CI-Ph)-C--__C-CH2-
009 (3-CI-Ph)-C=C-CHz-
010 (3-B r-P h )-C---C-C H 2-
011 (3-F-Ph)-C=C-CH2-
012 (3-CH3-Ph)-C=C-CH2-
013 (2,4-di-CI-Ph)-C=C-CH2-
014 (3,4-di-CI-Ph)-C-_-C-CH2-
015 (3,4-di-F-Ph)-C---C-CH2-
016 (3-CH3-4-CI-Ph)-C---C-CH2-
017 (3-CH3-4-Br-Ph)-C--_C-CH2-
018 (3-CF3-Ph)-C=C-CHZ-
019 (4-C F30-P h)-C---C-C H2-
020 (4-Et-Ph)-C---C-CH2-
021 [4-(CH3)3C-Ph]-C---C-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-51
022 (4-CH2=CH-Ph)-C--__C-CH2-
023 (4-CH_--C-Ph)-C---C-CH2-
024 (4-CH3-CO-Ph)-C--__C-CHz-
025 (4-CH300C-Ph)-C--__C-CH2-
026 (4-CH30-Ph)-C=C-CH2-
027 ~ ~ _ CH2-
028
- CH2_
S
029
N~ ~ - CH2-
030
~CH2-
N
031 Ph-(CH3)CH-
032 Ph-(CH3)zC-
033 (3-F-Ph)-CH2-
034 (4-Br-Ph)-CH2-
035 (4-J-Ph)-CH2-
036 (4-CH3-Ph)-CH2-
037 (4-CH30-Ph)-CH2-
038 (4-CF30-Ph)-CH2-
039 (4-F-Ph)-CH2-
040 (2,4-di-F-Ph)-CHz-
041 (3,4-di-F-Ph)-CHz-
042 (3,4-di-Br-Ph)-CH2-
043 (3,4-di-CI-Ph)-CH2-
044 (3-CI-4-CH3-Ph)-CH2-
045 (3-CH3-4-CI-Ph)-CH2-
046 (2,4,5-tri-CI-Ph)-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-52-
047 CH2-
048 ~ ~ CH2_
049
CHz-
050
CI S CH2-
051
Br S CH2-
052 Br
Br S CH2-
053
CH2-
N
054
CI ~ ~ CH2
N
055 CI
CF3 ~ ~~CH2-
-N
056 ~ N~ CH2
057 Ph-CH=CH-CHz-
058 (4-CI-Ph)-CH=CH-CH2-
059 (4-F-Ph)-CH=CH-CH2-
060 (4-Br-Ph)-CH=CH-CH2-
061 (3-CF3-Ph)-CH=CH-2-
062 Ph-CH2-CH2-
063 Ph-(CHz)2-CHZ-
064 (4-CI-Ph)-(CH2)2-CH2-
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-53-
065 (4-Br-Ph)-(CH2)2-CH2-
066 Ph-O-CH2-CH2-
067 (4-CI-Ph)-O-CH2-CH2-
068 (4-F-Ph)-O-CH2-CH2-
069 (4-Br-Ph)-O-CH2-CH2-
070 (3-F-Ph)-O-CH2-CH2-
071 (3,4-di-CI-Ph)-O-CH2-CH2-
072 (4-CI-Ph)-O-(CH3)CH-CH2-
073 (3,4-di-CI-Ph)-O-(CH3)CH-CH2-
074 Ph-N(CH3)-CH2-CH2-
075 Ph-N(CH2-CH3)-CH2-CH2-
076 Ph-S-CH2-CH2-
077 (4-CI-Ph)-S-CH2-CH2-
Formulations may be prepared analogously to those described in, for example,
W O 95/30651.
Biological Examples
D-1: Action against Plasmopara viticola (downy mildew) on vines
week old grape seedlings cv. Gutedel are treated with the formulated test
compound in a
spray chamber. One day after application grape plants are inoculated by
spraying a
sporangia suspension (4 x 104 sporangia/ml) on the lower leaf side of the test
plants. After
an incubation period of 6 days at +21 °C and 95% r. h. in a greenhouse
the disease
incidence is assessed.
Compounds of Tables 1 to 16 exhibit a good fungicidal action against
Plasmopara viticola
on vines. Compounds A1.3 and A1.4 at 200 ppm inhibit fungal infestation in
this test to a
least 80%, while under the same conditions untreated control plants are
infected by the
phytopathogenic fungi to over 80%.
CA 02403563 2002-09-19
WO 01/79159 PCT/EPO1/04202
-54-
D-2: Action against Phytophthora late blight) on tomato plants
3 week old tomato plants cv. Roter Gnom are treated with the formulated test
compound in
a spray chamber. Two day after application the plants are inoculated by
spraying a
sporangia suspension (2 x 104 sporangia/ml) on the test plants. After an
incubation period
of 4 days at +18~C and 95% r. h. in a growth chamber the disease incidence is
assessed.
Compounds of Tables 1 to 16 exhibit a long-lasting effect against fungus
infestation.
Compounds A1.3 and A1.4 at 200 ppm inhibit fungal infestation in this test to
a least 80%,
while under the same conditions untreated control plants are infected by the
phytopathogenic fungi to over 80%.
D-3 : Action against Phytophthora (late blight on potato plants
week old potato plants cv. Bintje are treated with the formulated test
compound in a spray
chamber. Two day after application the plants are inoculated by spraying a
sporangia
suspension (14 x 104 sporangia/ml) on the test plants. After an incubation
period of 4 days
at +18°C and 95% r. h. in a growth chamber the disease incidence is
assessed.
Fungal infestation is effectively controlled with compounds of Tables 1 to 16.
